A case of lupus-like glomerulonephritis in an HIV patient with nephrotic range proteinuria, purpura, and elevated IgA level.

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Yang, Jihyun; Seo, Min Young; Kim, Ki Tae; Lee, Jun Yong; Kim, Sun-Chul; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won-Yong; Kim, Hyoung-Kyu; Won, Nam Hee; Cha, Ran-Hui; Cho, Eunjung

2014-01-01

Human immunodeficiency virus (HIV) infection is growing medical concern worldwide. There are many types of glomerulonephritis which are associated with HIV infection. We report a case of a 53-year-old Korean man with an HIV infection, who was developed nephritic range proteinuria and purpura with elevated IgA level rasing a possibility of Henoch-Schölein Purpura (H-S purpura). However, renal biopsy showed "lupus-like feature" glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. Although baseline renal function was maintained without further need for maintenance dialysis following anti-retroviral therapy (ART) and steroid, patient died from uncontrolled gastrointestinal bleeding.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

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Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

2017-09-01

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated

Kidney disease in lupus is not always 'lupus nephritis'

NARCIS (Netherlands)

H.J. Anders (Hans-Joachim); J.J. Weening (Jan)

2013-01-01

textabstractIn lupus erythematosus, elevated serum creatinine levels and urinary abnormalities implicate a kidney disorder, which may not always be lupus nephritis as defined by the current classification of the International Society of Nephrology/Renal Pathology Society. The signs of renal

Socioeconomic status and organ damage in Mexican systemic lupus erythematosus women.

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Mendoza-Pinto, C; Méndez-Martínez, S; Soto-Santillán, P; Galindo Herrera, J; Pérez-Contreras, I; Macías-Díaz, S; Taboada-Cole, A; García-Carrasco, M

2015-10-01

The objective of this cross-sectional study was to determine relationships between socioeconomic status and organ damage in Mexican systemic lupus erythematosus (SLE) patients. Demographic and clinical variables were assessed. Socioeconomic status was evaluated using the Graffar method and monthly household income. Lupus activity and organ damage were measured using the SLE disease activity scale, validated for the Mexican population (Mex-SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scale. The 143 Mexican female SLE patients included (mean age 40.1 ± 8.9 years, mean disease duration 8.9 ± 6.3 years) had a mean monthly household income of $ 407.2 ± 326.5. According to the Graffar index, 18.9%, 52.5%, and 28.7% had high/medium-high, medium, and medium-low/low socioeconomic status, respectively. Organ damage was observed in 61 patients (42.7%). Patients with organ damage had lower monthly household incomes ($241.4 ± 152.4 vs. $354.8 ± 288.3) and were more frequently unemployed (57.3% vs. 35.3%; p = 0.01) than those without. Low monthly income was not associated with lupus activity or self-reported health status. In the adjusted multivariate analysis, low monthly income ( < $300) was associated with organ damage. In conclusion, low income may be associated with organ damage in Mexican SLE patients. © The Author(s) 2015.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

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Zhang, Chen-Xing; Cai, Li; Shao, Kang; Wu, Jing; Zhou, Wei; Cao, Lan-Fang; Chen, Tong-Xin

2018-05-01

Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1β, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus

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Yong JL

2013-02-01

Full Text Available Jim LC Yong,1,2 Murray C Killingsworth,1–3 Ken Lai1,21Department of Anatomical Pathology, Sydney South West Pathology Service, 2University of Western Sydney, School of Medicine, 3University of New South Wales, Faculty of Medicine, Sydney, New South Wales, AustraliaPurpose: The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes.Methods: Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander.Results: Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease.Conclusion: Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there

RENAL DAMAGE WITH MALIGNANT NEOPLASMS

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I. B. Kolina

2015-01-01

Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus.

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Yong, Jim Lc; Killingsworth, Murray C; Lai, Ken

2013-01-01

The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE) are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes. Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander. Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease. Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there was no relationship between sex, race, or age and severity of disease.

Imaging of systemic lupus erythematosus. Part II: Gastrointestinal, renal, and musculoskeletal manifestations

International Nuclear Information System (INIS)

Goh, Y.P.; Naidoo, P.; Ngian, G.-S.

2013-01-01

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that has a relapsing and remitting course. It has a wide range of presentations with various organ manifestations. In this review, we have compiled the radiological findings of gastrointestinal, renal, and musculoskeletal manifestations of SLE.

Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL).

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Banfi, G; Bertani, T; Boeri, V; Faraggiana, T; Mazzucco, G; Monga, G; Sacchi, G

1991-08-01

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

The Pathogenesis of Lupus Nephritis

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Lech, Maciej

2013-01-01

Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

Toll-like receptor activation in the pathogenesis of lupus nephritis.

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Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

2017-12-01

The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

Are Toll-Like Receptors and Decoy Receptors Involved in the Immunopathogenesis of Systemic Lupus Erythematosus and Lupus-Like Syndromes?

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Giuliana Guggino

2012-01-01

Full Text Available In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR and decoy receptors (DcR involved in the generation of systemic lupus erythematosus (SLE and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE.

A Cutaneous Lupus Erythematosus-Like Eruption Induced by Hydroxyurea.

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Yanes, Daniel A; Mosser-Goldfarb, Joy L

2017-01-01

Hydroxyurea is a medication with many well-described cutaneous side effects, notably the dermatomyositis-like eruption known as hydroxyurea dermopathy. Although systemic lupus erythematosus has been reported with hydroxyurea use, cutaneous lupus has not. We report a novel case of chronic cutaneous lupus induced by hydroxyurea and propose that this is a side effect that is distinct from hydroxyurea dermopathy. © 2016 Wiley Periodicals, Inc.

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

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Zamansky, G B

1986-08-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells.

Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

International Nuclear Information System (INIS)

Zamansky, G.B.

1986-01-01

The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

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Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

2017-11-01

Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

Purtscher-like retinopathy in systemic lupus erythematosus.

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Wu, Chan; Dai, Rongping; Dong, Fangtian; Wang, Qian

2014-12-01

To investigate clinical characteristics of Purtscher-like retinopathy and its clinical implications among patients with systemic lupus erythematosus (SLE). Observational case series. setting: Tertiary medical center. patient population: Patients with SLE who were diagnosed with Purtscher-like retinopathy between 2002 and 2013. observation procedures: Assessment and follow-up in the ophthalmology department. main outcome measure: Visual acuity and funduscopic examination at presentation and at 6 month follow-up, with analysis of the association between Purtscher-like retinopathy and other systemic involvement of SLE and overall disease activity. Among 5688 patients with SLE evaluated, 8 cases of Purtscher-like retinopathy were diagnosed. Typical fundus abnormalities included Purtscher flecken, cotton-wool spots, retinal hemorrhages, macular edema, optic disk swelling, and a pseudo-cherry red spot. Fluorescein angiography abnormalities included areas of capillary nonperfusion corresponding to the retinal whitening, late leakage, peripapillary staining, precapillary occlusion, and slower filling of vessels. The prevalence of central nervous system lupus was significantly higher among those with Purtscher-like retinopathy (6/8) than among 240 patients randomly sampled from those without Purtscher-like retinopathy. A very high SLE Disease Activity Index (≥20) was present in all 8 patients with Purtscher-like retinopathy. All patients received corticosteroids combined with immunosuppressants. For the majority of patients, optic atrophy developed during follow-up with persistent low visual acuity. As a rare and severe ophthalmic complication of SLE, Purtscher-like retinopathy was associated with central nervous system lupus and highly active disease. Visual acuity recovery was usually poor despite prompt treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years.

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Taraborelli, M; Cavazzana, I; Martinazzi, N; Lazzaroni, M Grazia; Fredi, M; Andreoli, L; Franceschini, F; Tincani, A

2017-10-01

Objective The aim of this study was to determine the prevalence, predictors and progression of organ damage in a monocentric cohort of systemic lupus erythematosus patients with a long follow-up. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index one year after diagnosis and every five years. Disease activity was measured by the systemic lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the follow-up. Univariate and multivariable analyses were used to detect items associated with damage. A total of 511 systemic lupus erythematosus patients (92% females, 95% Caucasian), prospectively followed from 1972 to 2014, were included. Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7% developed mild/moderate damage, while 19.5% showed severe damage. Damage was evident in 40% of 511 patients one year after diagnosis, and its prevalence linearly increased over time. Longer disease duration, higher SLEDAI, severe Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated with organ damage. No associations between damage and autoantibodies, including anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway, antiphospholipid syndrome and anticardiolipin antibodies predicted the development of neuropsychiatric damage. The ocular, musculoskeletal and neuropsychiatric systems were the most frequently damaged organs, with a linear increase during follow-up. Conclusion A high rate of moderate and severe damage has been detected early in a wide cohort of young lupus patients, with a linear trend of increase over time. Disease activity and long duration of disease predict damage, while antiphospholipid antibodies play a role in determining neuropsychiatric damage.

Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis.

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Maloney, K C; Ferguson, T S; Stewart, H D; Myers, A A; De Ceulaer, K

2017-11-01

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and

A clinico-pathological study of lupus nephritis based on the International Society of Nephrology-Renal Pathology Society 2003 classification system.

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Satish, Suchitha; Deka, Pallavi; Shetty, Manjunath Sanjeev

2017-01-01

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Renal involvement is a major determinant of the prognosis of SLE. The histological classification of LN is a key factor in determining the renal survival of patients with LN. Prompt recognition and treatment of renal disease are important, as early response to therapy is correlated with better outcome and renal biopsy plays an important role in achieving this. The objective of this study was to correlate the clinical and laboratory findings with histopathological classes of LN as per the 2003 International Society of Nephrology-Renal Pathology Society (ISN/RPS) classification system. Fifty-six patients with SLE, undergoing a renal biopsy for renal dysfunction were studied. The comparison of data from multiple groups was made by Pearson's Chi-square test and between two groups by independent samples t -test. The values of P renal biopsy. Since renal morphology may predict long-term prognosis, and no clinical or laboratory feature uniformly predicts prognosis, it is important to study the constellation of features in LN for better patient management.

Cardiovascular risk in lupus nephritis: Do renal disease-related and other traditional risk factors play a role?

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Inoshi Atukorala

2015-01-01

Full Text Available This study was performed to evaluate the prevalence of thickened carotid intima media thickness (CIMT in a Sri Lankan cohort of lupus nephritis (LN patients and to identify associations between traditional cardiovascular disease (CVD and LN-related risk factors with increased CIMT. Consecutive patients with biopsy-proven LN were evaluated for conventional CVD risk factors, renal parameters and extent of organ involvement in this cross-sectional study. Current disease activity and damage were assessed by the British Isles Lupus Activity Group (BILAG score and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR damage index, respectively. CIMT was assessed by B Mode grey scale ultrasonography. Increased CIMT was defined as CIMT more than the 75th percentile based on cutoffs from the "Carotid Atherosclerosis Progression Study." Forty patients (98% female, with a mean age of 38 years (age range of 20-50 and of South Asian descent, were evaluated. The mean duration of disease of 6.15 years (SD = 4.66. The overall prevalence of cardiovascular events was low and included previous acute coronary syndromes in 7.5%, stable angina in 5%, cerebrovascular accidents in 7.5% and transient ischemic attacks in 2.5% of the patients; 72.5% had hypertension (HTN [mean blood pressure (BP 140/80 mm Hg]; 32.5% had dyslipidemias (mean serum cholesterol 5.9; SD = 5.6 and 25% had diabetes (mean blood sugar 103.7; SD = 15.6. Forty percent were obese and 20% were overweight (Asian cutoffs. Increased CIMT (57.5% and atherosclerotic plaques (15.36% indicated a high CVD risk in this cohort. Diabetes (P = 0.016, HTN (P = 0.002, dyslipidemia (P = 0.002 and obesity (P = 0.048 were associated with thickened CIMT. The only LN-related risk factor associated with thickened CIMT (P <0.05 was the SLICC/ACR damage index. The independent predictors of thickened CIMT determined by logistic regression analysis were HTN and dyslipidemia.

Outcome of childhood lupus nephritis in Saudi children

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Sulaiman Mohammed Al-Mayouf

2017-01-01

Full Text Available Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE. All patients with childhood lupus nephritis (cLN proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD. Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI, and death related to SLE was determined. A total of 84 (72 females cLN patients with follow-up duration of 9.3 years (±5.2 were included in this study. The mean current age was 19.4 years (±5.5 and mean age at onset was 9.2 years (±2.4. The most frequent histopathological class was proliferative glomerulonephritis (64.3% followed by membranous nephritis (27.4%. The mean activity and chronicity indices were 5.9 (±3.9 and 2.9 (±2.2, respectively. Renal microthrombosis was found in 9 (10.7% patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197 and the mean protein/ creatinine ratio was 0.8 (± 1.1 while the mean total pSDI was 1.9 (±1.9 and mean renal SDI was 0.7 (±1.1. Sixteen (19% patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

Male lupus: a diagnosis often delayed--a case series and review of the literature.

LENUS (Irish Health Repository)

Ambrose, N L

2012-02-01

INTRODUCTION: Systemic lupus erythematosus (SLE) is an auto-immune disease that is characterised by autoantibody production. Male lupus is rare, apart from at either end of the age spectrum. AIM: In this series, we review the histories of six male lupus patients attending our service. RESULTS: Our patients presented in middle age and tended to develop haematological abnormalities, renal involvement and neurological manifestations which preceded the onset of their skin and joint complaints. Our patients accrued damage rapidly and overall did badly. They tended to respond sub-optimally to standard treatments. These cases highlight the need an increased awareness that male SLE patients present with a wide variety of symptoms, and that they accrue damage quickly. There is a need for timely diagnosis and appropriate initiation of treatment. This may help avoid preventable organ damage and increase the survival of men with SLE.

Prognostic factors in lupus nephritis

DEFF Research Database (Denmark)

Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

2006-01-01

To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis.......To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis....

Quantitative immunofluorescence microscopy of renal glomeruli from mice exhibiting murien lupus erythematosus

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Jensen, R H [Lawrence Livermore Lab., CA; Greenspan, J S; Moore, D II; Talal, N; Roubinian, J R

1981-01-01

Pathologic changes in renal glomeruli of mice with systemic murine lupus erythematosus were quantified using microfluorophotometry. Cryostat sections were taken from kidneys of affected mice, stained with fluorescein-conjugated anti-mouse immunoglobulin, and the extent of immune complex glomerulonephritis was determined. A subjective microscopic examination procedure, which has been used previously, was compared with quantitative microfluorophotometry and a close correlation between the results using each of the two methods was found. Since the microfluorometric procedure measures the total fluorescence per glomerulus, subjective microscopy must estimate that same quantity in a linear fashion. The present advance in measuring capability indicates good potential for rapid, quantitive measurements for further studies on systemic lupus erythematosus, and on other tissue sections stained with fluorescent antibodies.

Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus.

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Gómez-Guzmán, Manuel; Jiménez, Rosario; Romero, Miguel; Sánchez, Manuel; Zarzuelo, María José; Gómez-Morales, Mercedes; O'Valle, Francisco; López-Farré, Antonio José; Algieri, Francesca; Gálvez, Julio; Pérez-Vizcaino, Francisco; Sabio, José Mario; Duarte, Juan

2014-08-01

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. © 2014 American Heart Association, Inc.

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

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Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

2015-08-01

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

Combination Therapy With Pulse Cyclophosphamide Plus Corticosteroids Improves Renal Outcome In Patients With Lupus Nephritis

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H. Mansouri Torghabeh

2005-08-01

Full Text Available Background: The prognosis of SLE is int1uenced by the onset of glomerulonephtitis. Clinical ttials in lupus nephritis have demonstrated that cyclophosphamide therapy is the superior regimen in the management oflupus nephritis for preserving renal function.Objective:The purpose of this study is to define the outcome of renal function with bolus pu lses of cyclophosphamide and steroid according to our protocol and also to determine an appropriate pattern of treatment of lupus nephritis. Methods: In this open-label clinical triaL to evaluate the results, the short-term prognosis and the rate of complications of an immunosuppressive regimen with corticosteroids and cyclophosphamide, twenty-five patients with biopsy-proven lupus nephritis were studied. Treatment was structured in 4 phases: I Induction with bolus methylprednisolone and cyclophosphamide. 2 Maintenance with oral prednisolone for 4 weeks and monthly cyclophosphamide pulses for 6 months. 3 Tapeting with reduction of prednisolone by 10% each month and continuing cyclophosphamide every other month till one year and for the second year every 3 months. 4 Discontinuation with oral prednisolone slowly tapered to the least effective daily dose and cyclophosphamide discontinued after 2 yr of therapy. We defined primary outcome measures according to these criteria: renal function return to normal limits or become stable, regression of systemic and local inflammatory symptoms. urine protein excretion h1lling below 0.3 gr/ elL or by at least SOo/c. RBC cast disappearance, C3, C4, Hb, and ESR return to notmallimits. Result: Twenty-three patients wi th lupus nephritis completed our therapeutic protocol. Renal biopsy was perfonned in 22 cases and indicated type IV in 20 patients (95.2%, and type V in 2 patients. After an average of 4+ 1.95 months 22 patients achieved remission (95.65% and only one case remained non-responsive. She became pregnant in her fourth month of therapy. Significant

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

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Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, plupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, plupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, plupus nephritis (plupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

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Bertoli, A M; Vilá, L M; Reveille, J D; Alarcón, G S

2008-04-01

To determine the features associated with acute onset systemic lupus erythaematosus (SLE). A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

Protocol renal biopsy in patients with lupus nephritis: a single center experience.

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Singh, Ametashver; Ghosh, Rabindranath; Kaur, Prabhjeet; Golay, Vishal; Pandey, Rajendra; Roychowdhury, Arpita

2014-07-01

Renal biopsy plays an indispensable role in the diagnosis and management of patients with lupus nephritis (LN). A number of studies have evaluated the role of a repeat biopsy in case of disease relapse or treatment unresponsiveness. We studied 40 patients with LN with renal biopsies performed at baseline and after six months of therapy. The baseline and protocol biopsies were compared with respect to histological class transformation, crescents, tubular atrophy, interstitial fibrosis and glomerulosclerosis. We also compared serum creatinine, hemoglobin, systemic lupus erythematosus disease activity index (SLEDAI) scores, 24-h urine protein excretion and C3levels as well as activity index (AI) and chronicity index (CI) at baseline and at six months. Comparison of means was made by paired t test, McNemar test and marginal homogeneity test (multinomial data). Histological class transformation was seen in 10 patients (25%). Intra-class progression to greater chronicity was seen in 10 other patients (25%).There was an increase in glomerulosclerosis, tubular atrophy, interstitial fibrosis and a reduction in cellularity, crescent formation and wire loop lesions in the protocol biopsy. A decline in AI (6.05 vs. 2.50, P protocol biopsy. Our study shows a trend toward greater chronicity in protocol biopsies in LN.

Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

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Simon J Freeley

Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

Mercury in Hair Is Inversely Related to Disease Associated Damage in Systemic Lupus Erythematosus

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William Crowe

2015-12-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune inflammatory disease, and environmental factors are proposed to exacerbate existing symptoms. One such environmental factor is mercury. The aim of this study was to investigate the relationship between exposure to mercury (Hg and disease activity and disease associated damage in Total Hg concentrations in hair and urine were measured in 52 SLE patients. Dental amalgams were quantified. Disease activity was assessed using three indexes including the British Isles Lupus Assessment Group Index (BILAG. Disease associated damage was measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLICC/ACR Damage Index. Pearson’s correlation identified a significant negative correlation between hair Hg and BILAG (r = −0.323, p = 0.029 and SLICC/ACR (r = −0.377, p = 0.038. Multiple regression analysis identified hair Hg as a significant predictor of disease associated damage as determined by SLICC/ACR (β = −0.366, 95% confidence interval (CI: −1.769, −0.155 p = 0.019. Urinary Hg was not related to disease activity or damage. Fish consumption is the primary route of MeHg exposure in humans and the inverse association of hair Hg with disease activity observed here might be explained by the anti-inflammatory effects of n-3 long chain polyunsaturated fatty acids also found in fish.

Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).

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Franklyn, Kate; Lau, Chak Sing; Navarra, Sandra V; Louthrenoo, Worawit; Lateef, Aisha; Hamijoyo, Laniyati; Wahono, C Singgih; Chen, Shun Le; Jin, Ou; Morton, Susan; Hoi, Alberta; Huq, Molla; Nikpour, Mandana; Morand, Eric F

2016-09-01

Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Validation of Systemic Lupus Erythematosus Diagnosis as the Primary Cause of Renal Failure in the US Renal Data System.

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Broder, Anna; Mowrey, Wenzhu B; Izmirly, Peter; Costenbader, Karen H

2017-04-01

Using American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria for systemic lupus erythematosus (SLE) classification as gold standards, we determined sensitivity, specificity, positive and negative predictive values (PPV and NPV) of having SLE denoted as the primary cause of end-stage renal disease (ESRD) in the US Renal Data System (USRDS). ESRD patients were identified by International Classification of Diseases, Ninth Revision codes in electronic medical records of 1 large tertiary care center, Montefiore Hospital, from 2006 to 2012. Clinical data were extracted and reviewed to establish SLE diagnosis. Data were linked by social security number, name, and date of birth to the USRDS, where primary causes of ESRD were ascertained. Of 7,396 ESRD patients at Montefiore, 97 met ACR/SLICC SLE criteria, and 86 had SLE by record only. Among the 97 SLE patients, the attributed causes of ESRD in the USRDS were 77 SLE and 12 with other causes (unspecified glomerulonephritis, hypertension, scleroderma), and 8 missing. Sensitivity, specificity, PPV, and NPV for SLE in the USRDS were 79%, 99.9%, 93%, and 99.7%, respectively. Of the 60 patients with biopsy-proven lupus nephritis, 44 (73%) had SLE as primary ESRD cause in the USRDS. Attribution of the primary ESRD causes among SLE patients with ACR/SLICC criteria differed by race, ethnicity, and transplant status. The diagnosis of SLE as the primary cause of ESRD in the USRDS has good sensitivity, and excellent specificity, PPV, and NPV. Nationwide access to medical records and biopsy reports may significantly improve sensitivity of SLE diagnosis. © 2016, American College of Rheumatology.

A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients.

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Chanprapaph, K; Sawatwarakul, S; Vachiramon, V

2017-10-01

Objective The aim of this study was to investigate the clinical features, laboratory findings, systemic manifestations, treatment and outcome of patients with bullous systemic lupus erythematosus in a tertiary care center in Thailand. Methods We performed a retrospective review from 2002 to 2014 of all patients who fulfilled the diagnostic criteria for bullous systemic lupus erythematosus to evaluate for the clinical characteristics, extracutaneous involvement, histopathologic features, immunofluorescence pattern, serological abnormalities, internal organ involvement, treatments and outcome. Results Among 5149 patients with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 15 developed vesiculobullous lesions. Ten patients had validation of the diagnosis of bullous systemic lupus erythematosus, accounting for 0.19%. Bullous systemic lupus erythematosus occurred after the diagnosis of systemic lupus erythematosus in six patients with a median onset of 2.5 months (0-89). Four out of 10 patients developed bullous systemic lupus erythematosus simultaneously with systemic lupus erythematosus. Hematologic abnormalities and renal involvement were found in 100% and 90%, respectively. Polyarthritis (40%) and serositis (40%) were less frequently seen. Systemic corticosteroids, immunosuppressants, antimalarials and dapsone offered resolution of cutaneous lesions. Conclusion Bullous systemic lupus erythematosus is an uncommon presentation of systemic lupus erythematosus. Blistering can occur following or simultaneously with established systemic lupus erythematosus. We propose that clinicians should carefully search for systemic involvement, especially hematologic and renal impairment, in patients presenting with bullous systemic lupus erythematosus.

Understanding lupus nephritis: diagnosis, management, and treatment options

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Mok CC

2012-05-01

Full Text Available Chi Chiu MokDepartment of Medicine, Tuen Mun Hospital and Center for Assessment and Treatment of Rheumatic Diseases, Pok Oi Hospital, Hong Kong, ChinaAbstract: Systemic lupus erythematosus (SLE predominantly affects women in their reproductive years. Renal disease (glomerulonephritis is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.Keywords: lupus, nephritis, nephropathy, glomerulonephritis, treatment, therapy, women

[Plasma cell dyscrasias and renal damage].

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Pasquali, Sonia; Iannuzzella, Francesco; Somenzi, Danio; Mattei, Silvia; Bovino, Achiropita; Corradini, Mattia

2012-01-01

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

A clinical study on localized renal damage from percutaneous nephroureterolithotomy

International Nuclear Information System (INIS)

Chiba, Yutaka; Orikasa, Seiichi

1988-01-01

To study the localized renal damage from percutaneous nephroureterolithotomy (PNL), 3 divided DMSA renal scintigraphy in 41 renal units and dynamic CT in 17 renal units were performed. 1) Localized renal damages corresponding to the nephrostomy tract estimated by 3 divided DMSA renal scintigraphy were almost recovered by 6 months after PNL in most cases. But in 17 of the 41 renal units (41 %), the postoperative renal scintigram showed low uptake or cold area at the nephrostomy tract. 2) In several cases which showed cold area in postoperative renal scintigram, dynamic CT showed linear or diffuse low density area with sclerotic cortical deformity at the posterior wall of the kidney. These results indicate that an anatomically proper site of the puncture and a smaller nephrostomy size are mandatory to minimize localized renal damage from PNL. (author)

Clearing the complexity: immune complexes and their treatment in lupus nephritis

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Catherine Toong

2011-01-01

Full Text Available Catherine Toong1, Stephen Adelstein1, Tri Giang Phan21Department of Clinical Immunology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, Australia; 2Immunology Program, Garvan Institute of Medical Research and St. Vincent’s Clinical School, University of New South Wales, Darlinghurst, NSW, AustraliaAbstract: Systemic lupus erythematosus (SLE is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.Keywords: immune complex, systemic lupus erythematosus, nephritis, therapy

Renal damage detected by DMSA, despite normal renal ultrasound, in children with febrile UTI.

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Bush, N C; Keays, M; Adams, C; Mizener, K; Pritzker, K; Smith, W; Traylor, J; Villanueva, C; Snodgrass, W T

2015-06-01

2011 American Academy of Pediatrics guidelines recommended renal-bladder ultrasound (RBUS) as the only evaluation after febrile urinary tract infection (FUTI) in infants aged 2-24 months. We determined the sensitivity, specificity, and false negative rate of RBUS to identify DMSA-detected renal damage in this age group as well as in older children. Consecutive patients referred to pediatric urology with a history of FUTI underwent DMSA ≥ 3 months after FUTI. Abnormal RBUS was defined as: Society of Fetal Urology hydronephrosis grades I-IV; hydroureter ≥ 7 mm; renal scar defined as focal parenchymal thinning; and/or size discrepancy ≥ 1 cm between kidneys. Abnormal DMSA was presence of any focal uptake defects and/or split renal function 24 months. RBUS had poor sensitivity (34%) and low positive predictive value (47%) to identify patients with renal damage. 99/149 (66%) children with renal damage on DMSA had normal RBUS. After FUTI, 66% of children with reduced renal function and/or renal cortical defects found by DMSA scintigraphy had a normal RBUS. Since abnormal DMSA may correlate with increased risk for VUR, recurrent FUTI and renal damage, our data suggest RBUS alone will fail to detect a significant proportion of patients at risk. The data suggest that imaging after FUTI should include acute RBUS and delayed DMSA, reserving VCUG for patients with abnormal DMSA and/or recurrent FUTI. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Wener, M.H.; Mannik, M.; Schwartz, M.M.; Lewis, E.J.

1987-01-01

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc)

Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins

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Helga Stopper

2010-10-01

Full Text Available Patients with end-stage renal disease (ESRD, whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-a. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling.

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Qing, Xiaoping; Chinenov, Yurii; Redecha, Patricia; Madaio, Michael; Roelofs, Joris Jth; Farber, Gregory; Issuree, Priya D; Donlin, Laura; Mcllwain, David R; Mak, Tak W; Blobel, Carl P; Salmon, Jane E

2018-04-02

Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and metalloprotease 17 (ADAM17), whose substrates, such as TNF-α and heparin-binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone Fcgr2b-/- mice from developing severe kidney damage without altering anti-double-stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR and TNF-α signaling in the kidney tissues. Unbiased transcriptome profiling of kidneys and kidney macrophages revealed that TNF-α and HB-EGF/EGFR signaling pathways are highly upregulated in Fcgr2b-/- mice, alterations that were diminished in the absence of iRhom2. Pharmacological blockade of either TNF-α or EGFR signaling protected Fcgr2b-/- mice from severe renal damage. Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression, with interstitial HB-EGF expression significantly associated with chronicity indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-α and EGFR signaling plays a crucial role in mediating irreversible kidney damage in LN, thereby uncovering a target for selective and simultaneous dual inhibition of 2 major pathological pathways in the effector arm of the disease.

Control of lupus nephritis by changes of gut microbiota.

Science.gov (United States)

Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

2017-07-11

Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

Toll-like receptor 9 suppresses lupus disease in Fas-sufficient MRL Mice.

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Kevin M Nickerson

Full Text Available Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background. By 30 weeks of age, Tlr9-deficient MRL/+ had more severe renal disease, increased T cell activation, and higher titers of anti-Sm and anti-RNA autoantibodies than Tlr9-intact animals, as had been the case in the MRL.Faslpr model. In addition, Tlr9-deficient MRL/+ mice had increased numbers of germinal center phenotype B cells and an increase in splenic neutrophils and conventional dendritic cell populations. Thus, the disease accelerating effects of Tlr9 deficiency are separable from those mediated by the Fas mutation in the lupus-prone MRL genetic background. Nonetheless, disease acceleration in Tlr9-deficient MRL/+ mice was phenotypically distinct from that in Fas-deficient counterparts, which has important implications.

Renal damage in vesicoureteral reflux associated to duplex systems

International Nuclear Information System (INIS)

Orellana, P.; Velasquez, C.; Baquedano, P.

2002-01-01

Duplex system (DS) is a common occurrence and it can be associated to a range of ureteral and renal anomalies draining the two poles of the duplex kidneys, as vesicoureteral reflux (VUR) in the lower moiety and ureterocele in the upper moiety. The VUR in a duplex system can be primary or secondary (associated to an ureterocele). The assessment of parenchymal uptake and function of the whole and separate parts of the kidneys is important for therapeutical decisions. Objective: To determine the presence of renal damage, by dimercaptosuccinic acid (DMSA) scintigraphy in children with a refluxing DS and if there any difference between primary and secondary reflux. Patients and Methods: 36 children; 23 girls and 13 boys, with VUR into completely duplicated collecting systems was studied retrospectively (37 RU with DS, 35 unilateral and 1 bilateral), with a mean age of 2.43 y.o. (range: 1 month-11y.o.). All of the children underwent ultrasonography, voiding cystourethrogram and renal static scintigraphy. Among the 37 RU with VUR, 25 had primary VUR and 12 had VUR secondary to the presence of an ureterocele. Ten out of the 36 children (27.8%) were evaluated due to antenatal diagnosis and the remaining 26 (72.2%) after urinary tract infection (UTI). Results: Seventy percent of the 37 RU with VUR into completely duplicated collecting systems had renal damage demonstrated by renal static scintigraphy. Among the 25 RU with primary VUR, 19 (76%) had renal damage, 6 with a complete absence of function in the lower moiety. In this group, 80% of children was studied due to an UTI at a mean age of 3.3 y.o. In the group of children with secondary VUR, we observed a lower moiety with renal damage in 6/12 (50%), in 4 of them associated with an abnormal upper moiety. 7 out of 12 children (58.3%) had an abnormal upper moiety, 4 of them with a damage in lower moiety too. One children presented with renal exclusion. Half of these children were studied due to UTI, at a mean age of 1 y

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

2009-01-01

Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice.

Science.gov (United States)

Muñoz-García, Begoña; Moreno, Juan Antonio; López-Franco, Oscar; Sanz, Ana Belén; Martín-Ventura, José Luis; Blanco, Julia; Jakubowski, Aniela; Burkly, Linda C; Ortiz, Alberto; Egido, Jesús; Blanco-Colio, Luis Miguel

2009-12-01

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. ApoE(-/-) mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/d), anti-TWEAK neutralizing mAb (1000 microg/kg/d), TWEAK plus anti-TWEAK antibody (10 microg TWEAK +1000 microg anti-TWEAK/kg/d), or nonspecific IgG (1000 microg/kg/d) daily for 9 days. In ApoE(-/-) mice, exogenous TWEAK administration in ApoE(-/-) mice induced activation of NF-kappaB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE(-/-) mice with an anti-TWEAK blocking mAb decreased NF-kappaB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid-rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with

Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

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Malemud Charles J

2004-10-01

Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

NARCIS (Netherlands)

van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

Lupus nephritis management guidelines compared.

Science.gov (United States)

Wilhelmus, Suzanne; Bajema, Ingeborg M; Bertsias, George K; Boumpas, Dimitrios T; Gordon, Caroline; Lightstone, Liz; Tesar, Vladimir; Jayne, David R

2016-06-01

In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The LupusQoL and associations with demographics and clinical measurements in patients with systemic lupus erythematosus.

Science.gov (United States)

McElhone, Kathleen; Castelino, Madhura; Abbott, Janice; Bruce, Ian N; Ahmad, Yasmeen; Shelmerdine, Joanna; Peers, Kate; Isenberg, David; Ferenkeh-Koroma, Ada; Griffiths, Bridget; Akil, Mohammed; Maddison, Peter; Gordon, Caroline; Teh, Lee-Suan

2010-11-01

Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE. A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA. All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak. HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

Background. Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in

DMPD: Toll-like receptor 9 in murine lupus: more friend than foe! [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18241699 Toll-like receptor 9 in murine lupus: more friend than foe! Yu P, Musette ...us: more friend than foe! PubmedID 18241699 Title Toll-like receptor 9 in murine lupus...P, Peng SL. Immunobiology. 2008;213(2):151-7. Epub 2007 Sep 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptor 9 in murine lup

Role of MYH9 and APOL1 in African and non-African populations with lupus nephritis

DEFF Research Database (Denmark)

Lin, C P; Adrianto, I; Lessard, C J

2012-01-01

) and African-Americans (AAs) (N = 407). Multiple peaks of association exceeding a Bonferroni corrected P-value of P ...Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by autoantibody production and organ damage. Lupus nephritis (LN) is one of the most severe manifestations of SLE. Multiple studies reported associations between renal diseases and variants in the non-muscle myosin...... heavy chain 9 (MYH9) and the neighboring apolipoprotein L 1 (APOL1) genes. We evaluated 167 variants spanning MYH9 for association with LN in a multiethnic sample. The two previously identified risk variants in APOL1 were also tested for association with LN in European-Americans (EAs) (N = 579...

Renal myogenic constriction protects the kidney from age-related hypertensive renal damage in the Fawn-Hooded rat

NARCIS (Netherlands)

Vavrinec, Peter; Henning, Robert H.; Goris, Maaike; Landheer, Sjoerd W.; Buikema, Hendrik; van Dokkum, Richard P. E.

Introduction:Intact myogenic constriction plays a role in renal blood flow autoregulation and protection against pressure-related (renal) injury. However, to what extent alterations in renal artery myogenic constriction are involved in development of renal damage during aging is unknown. Therefore,

Discoid Lupus Erythematosus

Science.gov (United States)

... Name: Category: Share: Yes No, Keep Private Discoid Lupus Erythematosus Share | Discoid lupus erythematosus (DLE) is a chronic skin condition of sores ... diagnosis because other conditions can look like discoid lupus erythematosus. If the skin biopsy shows discoid lupus erythematosus, ...

Renal tissue damage induced by focused shock waves

Science.gov (United States)

Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

1990-07-01

Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

Tubular overexpression of gremlin induces renal damage susceptibility in mice.

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Alejandra Droguett

Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

Lúpus eritematoso sistêmico e tuberculose renal: descrição de nove Casos Systemic lupus erythematosus and renal tuberculosis: description of nine cases

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Daniela Cabral de Sousa

2008-02-01

Full Text Available OBJETIVO: O presente estudo tem por objetivo principal descrever uma série de nove casos de tuberculose (TB renal em pacientes portadores de lúpus eritematoso sistêmico (LES ocorridos em um período de seis anos em um hospital terciário do Nordeste brasileiro. MÉTODOS: Foram identificados nove pacientes portadoras de LES com baciloscopia e/ou cultura de urina positivas para Mycobacterium tuberculosis no período de outubro de 1998 a novembro de 2004, por intermédio dos registros do Serviço de Microbiologia do Hospital Universitário Walter Cantídio. Foram coletados dados demográficos, dados sobre o LES e sobre a TB renal das respectivas pacientes. RESULTADOS: Todas as pacientes eram do sexo feminino, com idade entre 19 e 58 anos. Quanto às características do LES, todas haviam tido nefrite lúpica em algum momento da evolução, das quais três haviam utilizado ciclofosfamida previamente à infecção. A dose média de prednisona antes do diagnóstico de TB renal variou entre 7, 5 e 20 mg/dia. O diagnóstico de TB renal foi feito por meio de cultura positiva em cinco pacientes e por intermédio de baciloscopia apenas em quatro pacientes. As manifestações laboratoriais mais freqüentes foram leucocitúria e hematúria. A recidiva da TB renal ocorreu em quatro pacientes. CONCLUSÃO: A ocorrência de TB renal em pacientes com LES deve ser suspeitada na presença de piúria estéril e/ou hematúria persistentes, em especial em populações de países em desenvolvimento.OBJECTIVE: The main objective of the present study was to describe a series of nine cases of renal tuberculosis (TB in patients diagnosed with systemic lupus erythematosus (SLE over a period of six years at a tertiary-level hospital in Northeastern Brazil. METHODS: Nine SLE patients with renal TB confirmed by bacterioscopy (n=4 or urine culture (n=5 positive for M. tuberculosis between October 1998 and November 2004 were sampled from the records of the microbiology

Lupus nephritis

African Journals Online (AJOL)

1991-03-02

Mar 2, 1991 ... will benefit from immunosuppressive therapy. Our study found hypertension, which persisted at the most recent follow-up, to be associated with a poor outcome, as was poor renal function both at biopsy and follow-up. Leaker er al. I found that survival in lupus nephritis is unaffected by age, sex, nephrotic ...

Case Report: Systemic Lupus Erythematosus Presenting as Acute ...

African Journals Online (AJOL)

We hereby report a case of a 20 year‑old female who presented to us in an acute hypoadrenal state and was found to have Systemic lupus erythematosus with renal involvement. Patient was successfully managed with steroids and improved clinically. Keywords: Addison's disease, Autoimmune diseases, Systemic lupus ...

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus

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Muscal, Eyal; De Guzman, Marietta M.; Myones, Barry L. [Texas Children' s Hospital, Baylor College of Medicine and Pediatric Rheumatology Center, Houston, TX (United States); Traipe, Elfrides; Hunter, Jill V. [Texas Children' s Hospital, Baylor College of Medicine and Diagnostic Imaging, Houston, TX (United States); Brey, Robin L. [University of Texas Health Science Center at San Antonio, Department of Neurology, San Antonio, TX (United States)

2010-07-15

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults. (orig.)

MR imaging findings suggestive of posterior reversible encephalopathy syndrome in adolescents with systemic lupus erythematosus

International Nuclear Information System (INIS)

Muscal, Eyal; De Guzman, Marietta M.; Myones, Barry L.; Traipe, Elfrides; Hunter, Jill V.; Brey, Robin L.

2010-01-01

Endothelial damage, hypertension and cytotoxic medications may serve as risk factors for the posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus. There have been few case reports of these findings in pediatric lupus patients. We describe clinical and neuroimaging findings in children and adolescents with lupus and a PRES diagnosis. We identified all clinically acquired brain MRIs of lupus patients at a tertiary care pediatric hospital (2002-2008). We reviewed clinical features, conventional MRI and diffusion-weighted imaging (DWI) findings of patients with gray- and white-matter changes suggestive of vasogenic edema and PRES. Six pediatric lupus patients presenting with seizures and altered mental status had MRI findings suggestive of PRES. In five children clinical and imaging changes were seen in conjunction with hypertension and active renal disease. MRI abnormalities were diffuse and involved frontal regions in five children. DWI changes reflected increased apparent diffusivity coefficient (unrestricted diffusion in all patients). Clinical and imaging changes significantly improved with antihypertensive and fluid management. MRI changes suggestive of vasogenic edema and PRES may be seen in children with active lupus and hypertension. The differential diagnosis of seizures and altered mental status should include PRES in children, as it does in adults. (orig.)

Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

DEFF Research Database (Denmark)

Krabbe, Simon; Gül, Cigdem; Andersen, Bjarne

2016-01-01

elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic...... lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations....

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

Science.gov (United States)

Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

2015-12-01

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Anti-IL-39 (IL-23p19/Ebi3) polyclonal antibodies ameliorate autoimmune symptoms in lupus-like mice

Science.gov (United States)

Wang, Xiaoqian; Zhang, Yu; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Shen, Beifen; Li, Yan; Xiao, He; Ma, Ning; Wang, Renxi

2018-01-01

The interleukin (IL)-12 family cytokines have been examined as therapeutic targets in the treatment of several autoimmune diseases. Our previous study showed that a novel IL-12 family cytokine, IL-39 (IL-23p19/Ebi3) mediates inflammation in lupus-like mice. In the present study, the effect of anti-mouse IL-39 polyclonal antibodies on autoimmune symptoms in lupus-like mice was investigated. Rabbit anti-mouse IL-39 polyclonal antibodies were produced by immunization with recombinant mouse IL-39, and purified using protein A chromatography. These antibodies were subsequently used to treat lupus-like mice. Flow cytometry, captured images, ELISA and H&E staining were used to determine the effect of anti-IL-39 polyclonal antibodies on inflammatory cells, autoantibody titers, proteinuria, infiltrating inflammatory cells and the structure of the glomerular region. The anti-IL-39 polyclonal antibodies effectively reduced the numbers of inflammatory cells, splenomegaly, autoantibody titers, proteinuria, infiltrating inflammatory cells, and restored the structure of the glomerular region in MRL/lpr mice. Taken together, these results suggested that anti-IL-39 polyclonal antibodies ameliorated autoimmune symptoms in lupus-like mice. Therefore, IL-39 may be used as a possible target for the treatment of systemic lupus erythematosus. PMID:29138852

Intracranial hypertension: A rare presentation of lupus nephritis.

Science.gov (United States)

Yadav, Praveen; Nair, Anishkumar; Cherian, Ajith; Sibi, N S; Kumar, Ashwini

2010-07-01

A 14-year-old male presented with bilateral papilledema, growth retardation and absent secondary sexual characters. He had a past history of fever, headache and fatigue of 6 months duration. The diagnosis of intracranial hypertension (IH) was confirmed by an increased intracranial pressure and normal neuroimaging studies of the brain, except for partial empty sella, prominent perioptic cerebrospinal fluid (CSF) spaces and buckling of optic nerves. Evaluation showed erythrocyte sedimentation rate (ESR) of 150 mm/hr, positive antinuclear antibody (ANA), anti dsDNA and anti ribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV S (A) confirming the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methyl prednisolone and cyclophosphamide was effective in normalizing the CSF pressure, resulting in express and dramatic resolution of symptomatology. In a case of IH, SLE must be considered. IH, growth retardation and absence of sexual characters may be presenting manifestations of a chronic systemic inflammatory disease like SLE. These manifestations may act as a pointer to associated advanced grades of LN, which can be totally asymptomatic and missed without a renal biopsy.

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

Directory of Open Access Journals (Sweden)

Mohamed Aboubakr

2014-01-01

Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort.

Science.gov (United States)

Durán-Barragán, S; McGwin, G; Vilá, L M; Reveille, J D; Alarcón, G S

2008-07-01

To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

Paradoxical effects of all-trans-retinoic acid on lupus-like disease in the MRL/lpr mouse model.

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Xiaofeng Liao

Full Text Available Roles of all-trans-retinoic acid (tRA, a metabolite of vitamin A (VA, in both tolerogenic and immunogenic responses are documented. However, how tRA affects the development of systemic autoimmunity is poorly understood. Here we demonstrate that tRA have paradoxical effects on the development of autoimmune lupus in the MRL/lpr mouse model. We administered, orally, tRA or VA mixed with 10% of tRA (referred to as VARA to female mice starting from 6 weeks of age. At this age, the mice do not exhibit overt clinical signs of lupus. However, the immunogenic environment preceding disease onset has been established as evidenced by an increase of total IgM/IgG in the plasma and expansion of lymphocytes and dendritic cells in secondary lymphoid organs. After 8 weeks of tRA, but not VARA treatment, significantly higher pathological scores in the skin, brain and lung were observed. These were accompanied by a marked increase in B-cell responses that included autoantibody production and enhanced expression of plasma cell-promoting cytokines. Paradoxically, the number of lymphocytes in the mesenteric lymph node decreased with tRA that led to significantly reduced lymphadenopathy. In addition, tRA differentially affected renal pathology, increasing leukocyte infiltration of renal tubulointerstitium while restoring the size of glomeruli in the kidney cortex. In contrast, minimal induction of inflammation with tRA in the absence of an immunogenic environment in the control mice was observed. Altogether, our results suggest that under a predisposed immunogenic environment in autoimmune lupus, tRA may decrease inflammation in some organs while generating more severe disease in others.

Histological Features of Antiphospholipid Nephropathy in Patients with Systemic Lupus Erythematosus

International Nuclear Information System (INIS)

Naseeb, F.; Arfaj, A. A..; Hamdani, A.; Parvez, K.; Mogairen, S. A.; Kfoury, H.

2015-01-01

Objective:To determine the histological features of renal biopsies of Systemic Lupus Erythematosus (SLE) patients with and without antiphospholipid antibodies in Saudi population. Study Design: Cross-sectional, comparative study. Place and Duration of Study: King Khalid University Hospital, Riyadh, Saudi Arabia, from January to December 2013. Methodology: Consecutive SLE patients admitted to King Khalid University Hospital, Riyadh for renal biopsy for evaluation of proteinuria or deterioration of renal function were recruited. SLE patients with renal involvement were divided in two groups. Group one included patients with positive APS antibodies and group two included patients with negative APS antibodies. The histological features of renal biopsies of the two patients groups were compared. Data was analyzed using simple statistical analysis. Results: The mean age of APS antibodies-positive patients was 30.37 ± 10.714 years while mean age of APS negative patients was 33.62 ± 11.717 years (p=0.224). Twenty five (83.33 percentage) patients were females and 5 (16.67 percentage) patients were males in APS positive patients while 42 (89.36 percentage) were females and 5 (10.63 percentage) were males in group two. Acute lesions like thrombotic microangiopathy were in 2 (6.7 percentage) of APS positive patients while chronic lesions like focal cortical atrophy was found in 6 (20 percentage) and fibrous intimal hyperplasia was found in 9 (30 percentage). Other significant histological findings in APS antibodies positive group were glomerular basement membrane wrinkling in 12 (40 percentage), glomerular double wall contour in 17 (56.7 percentage), fibrous adhesions in 11 (36.7 percentage) patients with APS antibodies. Conclusion:Systemic Lupus Erythematosus (SLE) patients with positive APS antibodies has specific histological findings suggesting an important role of APS antibodies in the pathogenesis of APS nephropathy. (author)

Anti-C1q antibodies in systemic lupus erythematosus

DEFF Research Database (Denmark)

Orbai, A-M; Truedsson, L; Sturfelt, G

2015-01-01

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information...... in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis....

Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis

International Nuclear Information System (INIS)

Lin Wanyu; Hsieh Jihfang; Tsai Shihchuan; Lan Joungliang; Cheng Kaiyuan; Wang Shyhjen

2000-01-01

Within nuclear medicine there is a trend towards quantitative analysis. Gallium renal scan has been reported to be useful in monitoring the disease activity of lupus nephritis. However, only visual interpretation using a four-grade scale has been performed in previous studies, and this method is not sensitive enough for follow-up. In this study, we developed a semi-quantitative method for gallium renal scintigraphy to find a potential parameter for the evaluation of lupus nephritis. Forty-eight patients with lupus nephritis underwent renal biopsy to determine World Health Organization classification, activity index (AI) and chronicity index (CI). A delayed 48-h gallium scan was also performed and interpreted by visual and semi-quantitative methods. For semi-quantitative analysis of the gallium uptake in both kidneys, regions of interest (ROIs) were drawn over both kidneys, the right forearm and the adjacent spine. The uptake ratios between these ROIs were calculated and expressed as the ''kidney/spine ratio (K/S ratio)'' or the ''kidney/arm ratio (K/A ratio)''. Spearman's rank correlation test and Mann-Whitney U test were used for statistical analysis. Our data showed a good correlation between the semi-quantitative gallium scan and the results of visual interpretation. K/S ratios showed a better correlation with AI than did K/A ratios. Furthermore, the left K/S ratio displayed a better correlation with AI than did the right K/S ratio. In contrast, CI did not correlate well with the results of semi-quantitative gallium scan. In conclusion, semi-quantitative gallium renal scan is easy to perform and shows a good correlation with the results of visual interpretation and renal biopsy. The left K/S ratio from semi-quantitative renal gallium scintigraphy displays the best correlation with AI and is a useful parameter in evaluating the disease activity in lupus nephritis. (orig.)

[Clinical guideline for the treatment of lupus nephritis and single-centre results of mycofenolate mofetil among patients with lupus nephritis in the National Institute of Rheumatology and Physiotherapy, Budapest].

Science.gov (United States)

Szabó, Melinda Zsuzsanna; Kiss, Emese

2016-08-01

The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30-30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385-1393.

The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury

NARCIS (Netherlands)

Leemans, Jaklien C.; Butter, Loes M.; Pulskens, Wilco P. C.; Teske, Gwendoline J. D.; Claessen, Nike; van der Poll, Tom; Florquin, Sandrine

2009-01-01

Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The

The proximal tubular cell, a key player in renal damage

NARCIS (Netherlands)

Timmeren, Mirjan Miranda van

2008-01-01

A decline in renal function is associated with the degree of proteinuria and with histological findings of glomerulosclerosis and interstitial fibrosis. Proteinuria is not only a marker of renal damage, but ultrafiltered proteins can be toxic to the kidney, thereby contributing to

Urinary tract infection in small children: the evolution of renal damage over time.

Science.gov (United States)

Swerkersson, Svante; Jodal, Ulf; Sixt, Rune; Stokland, Eira; Hansson, Sverker

2017-10-01

Our objective was to analyze the evolution of kidney damage over time in small children with urinary tract infection (UTI) and factors associated with progression of renal damage. From a cohort of 1003 children UTI, a retrospective analysis of 103 children was done. Children were selected because of renal damage at index 99m Tc-dimercaptosuccinic acid (DMSA) scintigraphy at least 3 months after UTI, and a late DMSA scan was performed after at least 2 years. Damage was classified as progression when there was a decline in differential renal function (DRF) by ≥4%, as regression when there was complete or partial resolution of uptake defects. Of 103 children, 20 showed progression, 20 regression, and 63 remained unchanged. There were no differences between groups regarding gender or age. In the progression group, 16/20 (80%) children had vesicoureteral reflux (VUR) grade III-V and 13 (65%) had recurrent UTI. In multivariable regression analysis, both VUR grade III-V and recurrent UTI were associated with progression. In the regression group, 16/20 (80%) had no VUR or grade I-II, and two (10%) had recurrent UTI. Most small children with febrile UTI do not develop renal damage and if they do the majority remain unchanged or regress over time. However, up to one-fifth of children with renal damage diagnosed after UTI are at risk of renal deterioration. These children are characterized by the presence of VUR grades III-V and recurrent febrile UTI and may benefit from follow-up.

Research Progress on Systemic Lupus Erythematosus Complicated with Infection

Directory of Open Access Journals (Sweden)

Zhang Weisan

2015-06-01

Full Text Available In recent years, in treatment standardization of systemic lupus erythematosus (SLE, infections and serious complications became the leading cause of death related to this disease, exceeding those of renal involvement and lupus encephalopathy. SLE coinfection is mainly related to defects in humoral immunity and cellular immunity, SLE disease activity, and doses of hormone and immune inhibitors.

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

Science.gov (United States)

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Acute macular neuroretinopathy associated with systemic lupus erythematosus.

Science.gov (United States)

Lee, D H; Lee, S C; Kim, M

2016-04-01

Acute macular neuroretinopathy (AMN) is a rare disorder that presents with abrupt visual change with wedge-shaped or flower-like lesions pointing towards the fovea. Ischemic insults to the retinal capillary plexus may be important for development of this disease. While many case reports have been published on AMN, none have described AMN in association with systemic lupus erythematosus (SLE). Here, we report a case of AMN associated with newly-diagnosed SLE. We speculate that in patients with lupus flares, immune complex-mediated vascular injury and microvascular thrombosis may disrupt the deep retinal capillary network, causing ischemic damages to the outer retina and leading to the development of AMN. AMN can develop in patients with lupus flares, and must be considered as an SLE-associated ophthalmologic complication. To the best of our knowledge, this is the first case report of AMN associated with SLE. © The Author(s) 2015.

Tc-99m mercaptoacetylglycine to evaluate renal damage after ESWL

International Nuclear Information System (INIS)

Schaub, T.; Witsch, U.; El Damanhoury, H.; Naegele-Woehrle, B.; Hahn, K.

1990-01-01

This paper evaluates renal damage after extracorporeal shock wave lithotripsy (ESWL) with a new Tc-99m renal imaging compound. Tc-99m mercaptoacetylglycine-3 (MAG3) sequential scintigraphy was performed on 113 patients. A gamma camera was used, and the studies were done within 2 days before and after ESWL for renal stones. Relative renal function and clearance were calculated. Seventy (62%) of the 113 patients had abnormal findings after ESWL that were not present before the treatment. In 56 patients (50%) intra- or perirenal lesions were seen on sequential scintigraphy. Forty-six patients (41%) had a decrease of the relative renal function of at least 3% without an increase of total renal function

Repair of uv damaged DNA in systemic lupus erythematosus. [Mice

Energy Technology Data Exchange (ETDEWEB)

Beighlie, D J; Teplitz, R L

1975-06-01

The NZB NZW hybrid mouse is an animal model of human systemic lupus erythematosus (SLE). Two breeding schemes were devised using NZB, NZW, B/W, and CBA mice, which permit definitive decisions regarding genetic and/or viral origin of the disease. It is proposed that at least two factors must be involved: a genetic abnormality producing hyper-responsiveness to nucleic acid antigens, and a DNA repair defect which results in liberation of DNA and RNA when cells are lethally injured. Evidence is presented for a DNA repair deficit in human SLE lymphocytes following in vitro irradiation with ultraviolet (uv) light. Lymphocytes from adult New Zealand and control mice were found to lack normal amounts of endonuclease necessary for repairing uv damage.

Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy

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Anna Czajka

2016-12-01

Full Text Available Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN, a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs and proximal tubular cells (HK-2 were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN.

Semi-quantitative evaluation of gallium-67 scintigraphy in lupus nephritis

Energy Technology Data Exchange (ETDEWEB)

Lin Wanyu [Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan); Dept. of Radiological Technology, Chung-Tai College of Medical Technology, Taichung (Taiwan); Hsieh Jihfang [Section of Nuclear Medicine, Chi-Mei Foundation Hospital, Yunk Kang City, Tainan (Taiwan); Tsai Shihchuan [Dept. of Nuclear Medicine, Show Chwan Memorial Hospital, Changhua (Taiwan); Lan Joungliang [Dept. of Internal Medicine, Taichung Veterans General Hospital, Taichung (Taiwan); Cheng Kaiyuan [Dept. of Radiological Technology, Chung-Tai College of Medical Technology, Taichung (Taiwan); Wang Shyhjen [Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan)

2000-11-01

Within nuclear medicine there is a trend towards quantitative analysis. Gallium renal scan has been reported to be useful in monitoring the disease activity of lupus nephritis. However, only visual interpretation using a four-grade scale has been performed in previous studies, and this method is not sensitive enough for follow-up. In this study, we developed a semi-quantitative method for gallium renal scintigraphy to find a potential parameter for the evaluation of lupus nephritis. Forty-eight patients with lupus nephritis underwent renal biopsy to determine World Health Organization classification, activity index (AI) and chronicity index (CI). A delayed 48-h gallium scan was also performed and interpreted by visual and semi-quantitative methods. For semi-quantitative analysis of the gallium uptake in both kidneys, regions of interest (ROIs) were drawn over both kidneys, the right forearm and the adjacent spine. The uptake ratios between these ROIs were calculated and expressed as the ''kidney/spine ratio (K/S ratio)'' or the ''kidney/arm ratio (K/A ratio)''. Spearman's rank correlation test and Mann-Whitney U test were used for statistical analysis. Our data showed a good correlation between the semi-quantitative gallium scan and the results of visual interpretation. K/S ratios showed a better correlation with AI than did K/A ratios. Furthermore, the left K/S ratio displayed a better correlation with AI than did the right K/S ratio. In contrast, CI did not correlate well with the results of semi-quantitative gallium scan. In conclusion, semi-quantitative gallium renal scan is easy to perform and shows a good correlation with the results of visual interpretation and renal biopsy. The left K/S ratio from semi-quantitative renal gallium scintigraphy displays the best correlation with AI and is a useful parameter in evaluating the disease activity in lupus nephritis. (orig.)

Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood-Onset Systemic Lupus Erythematosus.

Science.gov (United States)

Borgia, R Ezequiel; Gerstein, Maya; Levy, Deborah M; Silverman, Earl D; Hiraki, Linda T

2018-04-01

To describe the features and treatment of macrophage activation syndrome (MAS) in a single-center cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare childhood-onset SLE manifestations and outcomes between those with and those without MAS. We included all patients with childhood-onset SLE followed up at The Hospital for Sick Children from 2002 to 2012, and identified those also diagnosed as having MAS. Demographic, clinical, and laboratory features of MAS and SLE, medication use, hospital and pediatric intensive care unit (PICU) admissions, as well as damage indices and mortality data were extracted from the Lupus database. Student's t-tests and Fisher's exact tests were used to compare continuous and categorical variables, respectively. We calculated incidence rate ratios of hospital and PICU admissions comparing patients with and those without MAS, using Poisson models. Kaplan-Meier survival analysis was used to examine the time to disease damage accrual. Of the 403 patients with childhood-onset SLE, 38 (9%) had MAS. The majority (68%) had concomitant MAS and SLE diagnoses. Fever was the most common MAS clinical feature. The frequency of renal and central nervous system disease, hospital admissions, the average daily dose of steroids, and time to disease damage were similar between those with and those without MAS. We observed a higher mortality rate among those with MAS (5%) than those without MAS (0.2%) (P = 0.02). MAS was most likely to develop concomitantly with childhood-onset SLE diagnosis. The majority of the MAS patients were successfully treated with corticosteroids with no MAS relapses. Although the numbers were small, there was a higher risk of death associated with MAS compared to SLE without MAS. © 2018, American College of Rheumatology.

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry.

Science.gov (United States)

Pego-Reigosa, José María; Lois-Iglesias, Ana; Rúa-Figueroa, Íñigo; Galindo, María; Calvo-Alén, Jaime; de Uña-Álvarez, Jacobo; Balboa-Barreiro, Vanessa; Ibáñez Ruan, Jesús; Olivé, Alejandro; Rodríguez-Gómez, Manuel; Fernández Nebro, Antonio; Andrés, Mariano; Erausquin, Celia; Tomero, Eva; Horcada Rubio, Loreto; Uriarte Isacelaya, Esther; Freire, Mercedes; Montilla, Carlos; Sánchez-Atrio, Ana I; Santos-Soler, Gregorio; Zea, Antonio; Díez, Elvira; Narváez, Javier; Blanco-Alonso, Ricardo; Silva-Fernández, Lucía; Ruiz-Lucea, María Esther; Fernández-Castro, Mónica; Hernández-Beriain, José Ángel; Gantes-Mora, Marian; Hernández-Cruz, Blanca; Pérez-Venegas, José; Pecondón-Español, Ángela; Marras Fernández-Cid, Carlos; Ibáñez-Barcelo, Mónica; Bonilla, Gema; Torrente-Segarra, Vicenç; Castellví, Iván; Alegre, Juan José; Calvet, Joan; Marenco de la Fuente, José Luis; Raya, Enrique; Vázquez-Rodríguez, Tomás Ramón; Quevedo-Vila, Víctor; Muñoz-Fernández, Santiago; Otón, Teresa; Rahman, Anisur; López-Longo, Francisco Javier

2016-07-01

To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The combination of two Sle2 lupus-susceptibility loci and Cdkn2c deficiency leads to T cell-mediated pathology in B6.Faslpr mice

Science.gov (United States)

Xu, Zhiwei; Croker, Byron P.; Morel, Laurence

2013-01-01

The NZM2410 Sle2c1 lupus susceptibility locus is responsible for the expansion of the B1a cell compartment and for the induction of T-cell induced renal and skin pathology on a CD95 deficient (Faslpr)-background. We have previously shown that deficiency in cyclin-dependent kinase inhibitor p18INK4c (p18) was responsible for the B1a cell expansion but was not sufficient to account for the pathology in B6.lpr mice. This study was designed to map the additional Sle2c1 loci responsible for autoimmune pathology when co-expressed with CD95 deficiency. The production, fine-mapping and phenotypic characterization of five recombinant intervals indicated that three interacting sub-loci were responsive for inducting autoimmune pathogenesis in B6.lpr mice. One of these sub-loci corresponds most likely to p18-deficiency. Another major locus mapping to a 2 Mb region at the telomeric end of Sle2c1 is necessary to both renal and skin pathology. Finally, a third locus centromeric to p18 enhances the severity of lupus nephritis. These results provide new insights into the genetic interactions leading to SLE disease presentation, and represent a major step towards the identification of novel susceptibility genes involved in T-cell mediated organ damage. PMID:23698709

The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort.

Science.gov (United States)

Conti, F; Ceccarelli, F; Perricone, C; Leccese, I; Massaro, L; Pacucci, V A; Truglia, S; Miranda, F; Spinelli, F R; Alessandri, C; Valesini, G

2016-06-01

Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). In the present study chronic damage was identified in about one third of SLE patients. The

Arteriovenous thrombosis in chronic renal failure patients receving renal replacement therapy

International Nuclear Information System (INIS)

Shoaib, M.; Naz, A.

2008-01-01

To determine the frequency of thrombotic complications and to identify factors associated with arteriovenous thrombosis in patients of chronic renal failure receiving renal replacement therapy. Of the 3000 patients evaluated, 61 End Stage Renal Disease (ESRD) patients on regular dialysis, having recent renal transplant, were selected for the study after informed consent. These patients had arteriovenous thrombosis with temporary central lines thrombosis and vascular access problems. Cases of congenital or acquired thrombotic disorders, e.g. with malignancy, DIC, liver disease, systemic lupus erythematosus or other immunologic diseases, pregnancy or women using oral contraceptives, were excluded. Similarly, patients taking any type of anticoagulant therapy during the preceding one week were not included in the study. Findings were recorded in a structured questionnaire. Laboratory analysis was done after clinical and radiological evaluation. Thrombophilia screening included antithrombin, protein C, protein S deficiencies and lupus anticoagulant. Forty-seven out of 61 patients selected were positive for thrombophilia screening with protein C deficiency in 26.2%, protein S deficiency in 16.3%, antithrombin in 5%, lupus anticoagulant in 13.1% and combined deficiency was observed in 16.3%. Of the 3000 patients, 61 with frequency of 2% were found to be deficient in one or had combined deficiency of these. Thus, the study of ESRD patients presenting with arteriovenous thromboembolism emphasizes the need to reconsider the perception that this clinical entity is rare and requires further studies. (author)

Systemic Lupus Erythematosus Presenting as Acute Adrenal ...

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hanumantp

presented to us with a history of anorexia, progressive darkening of the face ... to us in an acute hypoadrenal state and was found to have Systemic lupus erythematosus with renal involvement. .... Textbook of Endocrinology. 11th ed. Saunders: ...

Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

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Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

2016-01-01

Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

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Shenavandeh, S; Habibi, S

2017-08-01

Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p  0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

Systemic Lupus Erythematosus (Lupus)

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... Lupus) English Español 繁體中文 한국어 tiếng Việt Systemic Lupus Erythematosus (Lupus) Basics In-Depth Download Download EPUB Download PDF What is it? Points To Remember About Systemic Lupus Erythematosus (Lupus) Lupus can affect many body parts, ...

4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

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Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

2014-02-01

We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

Mesenchymal Stem Cells Control Complement C5 Activation by Factor H in Lupus Nephritis

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Haijun Ma

2018-06-01

Full Text Available Lupus nephritis (LN is one of the most severe complications of systemic lupus erythematosus (SLE caused by uncontrolled activation of the complement system. Mesenchymal stem cells (MSCs exhibit clinical efficacy for severe LN in our previous studies, but the underlying mechanisms of MSCs regulating complement activation remain largely unknown. Here we show that significantly elevated C5a and C5b-9 were found in patients with LN, which were notably correlated with proteinuria and different renal pathological indexes of LN. MSCs suppressed systemic and intrarenal activation of C5, increased the plasma levels of factor H (FH, and ameliorated renal disease in lupus mice. Importantly, MSCs transplantation up-regulated the decreased FH in patients with LN. Mechanistically, interferon-α enhanced the secretion of FH by MSCs. These data demonstrate that MSCs inhibit the activation of pathogenic C5 via up-regulation of FH, which improves our understanding of the immunomodulatory mechanisms of MSCs in the treatment of lupus nephritis. Keywords: Lupus nephritis, C5, MSCs, FH

Failure to thrive and nephrocalcinosis due to distal renal tubular acidosis: A rare presentation of pediatric lupus nephritis.

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Nandi, Madhumita; Das, Mrinal Kanti; Nandi, Sukanta

2016-01-01

A 9-year-old female child was initially diagnosed of having nephrocalcinosis with distal renal tubular acidosis (dRTA) while investigating for short stature. She later on developed features of nephrotic syndrome (NS) while on treatment for RTA. Investigation for the cause of NS revealed very strong serological evidence in favor of systemic lupus erythematosus (SLE). Histopathological confirmation could not be done due to bilateral severely contracted kidneys. There are a few case reports of dRTA as the presentation of SLE, but nephrocalcinosis with dRTA with subsequent manifestation of SLE has hitherto not been reported in literature.

Toxic Epidermal Necrolysis-Like Lesions and Systemic Lupus Erythematosus Possibly Triggered by Sulfasalazine

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Simon Krabbe

2016-01-01

Full Text Available This case report describes a patient with arthritis of the large joints, bilateral sacroiliitis, and positive anti-SSA and anti-dsDNA antibody, who received sulfasalazine and shortly thereafter became critically ill. He developed toxic epidermal necrolysis, hemolytic anemia, lymphopenia, markedly elevated ferritin, and muscle wasting. A diagnosis of systemic lupus erythematosus was made, and mycophenolate mofetil and systemic glucocorticoids brought this severe disease under control. Toxic epidermal necrolysis-like lesions and hemophagocytic syndrome have been reported as manifestations of systemic lupus erythematosus. This patient possibly had spondyloarthritis or an undifferentiated connective tissue disease at presentation, and we suggest, based on the timing of events, that sulfasalazine may have acted as a trigger of the severe disease manifestations.

Plasma ficolin levels and risk of nephritis in Danish patients with systemic lupus erythematosus

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Tanha, Nima; Pilely, Katrine; Faurschou, Mikkel

2017-01-01

Given the scavenging properties of ficolins, we hypothesized that variation in the plasma concentrations of the three ficolins may be associated with development of lupus nephritis (LN), type of LN, end-stage renal disease (ESRD), and/or mortality among patients with systemic lupus erythematosus...

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

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Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE

Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

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Kapoor, T M; Mahadeshwar, P; Nguyen, S; Li, J; Kapoor, S; Bathon, J; Giles, J; Askanase, A

2017-12-01

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm 3 . The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects

Prognosis and predictors of convulsion among pediatric lupus nephritis patients

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Beiraghdar, Fatemeh; Einollahi, Behzad; Taheri, Saeed; Panahi, Yunes; Maddani, Abbas; Esfahani, Taher; Sharifi-Bonab, Mir Mohsen

2009-01-01

In this study, we aimed to analyze features and outcome of convulsion in pediatric lupus nephritis patients. We retrospectively reviewed data of 14 Iranian children with lupus nephritis who developed seizures and compared them with a group of the same number of well matched pediatric lupus nephritis patients. Higher serum creatinine levels and higher frequencies of anemia and lymphopenia were observed in the convulsion group. Multivariable logistic regression analysis revealed that the only risk factor for development of convulsion in pediatric lupus patients with nephritis was lymphopenia. Survival analysis showed that convulsion had no impact on patient and renal function outcomes in our pediatric lupus nephritis subjects. In conclusion, we found that lymphopenia is a predictive factor for convulsion occurrence in our patients and special attention to neurological status assessment may be needed in this situation. (author)

Summary of the mechanism of U-induced renal damage and its biochemical studies

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Chen Rusong

1994-05-01

In China studies on the toxicology of uranium were systematically conducted from the 1960's. Among them the studies of the change of biochemical indicators of U-induced renal damage were involved. On the basis of summarizing the relevant information of our country and the study progress of biochemical methods in recent years, the mechanism of U-induced renal damage and its biochemical basis, the behavior of uranium in kidney and the recent progress to detect renal damage with several biochemical indexes (such as α 1 -or β 2 -microglobulin, N-acetyl-β-D-glucosaminidase and alanine aminopeptidase etc.) are introduced respectively. Finally, the evaluation on the biochemical basis for acquired tolerance to U in kidney is performed. It should be noted that from the clinical viewpoint the tolerance cannot be considered as a practical measure of protection

Prolidase deficiency: it looks like systemic lupus erythematosus but it is not

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Klar, Aharon; Navon-Elkan, Paulina; Rubinow, Alan

2010-01-01

Three siblings with recalcitrant leg ulceration, splenomegaly, photosensitive rash, and autoantibodies were suspected of having prolidase deficiency. Urine was checked for iminodipeptiduria, fibroblasts were cultured and analyzed for prolidase activity, and DNA was extracted for identifying the c...... was diagnosed in siblings with skin ulceration autoantibodies and a lupus-like disease. A novel nonsense mutation was found, associated with the severe outcome of our patients....

Systemic lupus erythematosus in a multi-ethnic cohort (LUMINA) XXXII: [corrected] contributions of admixture and socioeconomic status to renal involvement.

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Alarcón, G S; Bastian, H M; Beasley, T M; Roseman, J M; Tan, F K; Fessler, B J; Vilá, L M; McGwin, G

2006-01-01

Renal involvement in systemic lupus erythematosus (SLE) is more frequent in minorities. We examined whether genetic or socioeconomic status (SES) explain these disparities in a large multiethnic (Hispanics from Texas and Puerto Rico, African Americans and Caucasians) SLE cohort. Renal involvement was defined as WHO Class II-V and/or proteinuria (> 0.5 g/24 h or 3+) attributable to SLE and/or abnormal urinary sediment, proteinuria 2+, elevated serum creatinine/ decreased creatinine clearance twice, 6 months apart present any time over the course of the disease. Ancestry informative markers (AIMS) were used to define the admixture proportions in each patient and group. Logistic regression models were examined to determine the percentage variance (R2) in renal involvement related to ethnicity that is explained by socio-economic status (SES) and admixture (adjusting for age, gender and disease duration, basic model). Four-hundred and fifty-nine (out of 575) patients were included; renal involvement occurred in 44.6% Texas Hispanics, 11.3% Puerto Rico Hispanics, 45.8% African Americans, 18.3% Caucasians. SES accounted for 14.5% of the variance due to ethnicity (after adjusting for basic model variables), admixture 36.8% and both, 12.2%; 45.9% of the variance remained unexplained. Alternative models for decreased glomerula filtration rate and end-stage renal disease were comparable in the distribution of the explanatory variables. Our data indicate that genetic factors appear to be more important than SES in explaining the ethnic disparities in the occurrence of renal involvement.

Renal biopsies in Johor: a 7-year study.

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Khoo, J J

2001-12-01

Consecutive renal biopsies received from 1994 to 2000 in Johor Bahru were reviewed. There were 441 cases, of which 407 were adequate biopsies (92.3%). Lupus nephritis formed the largest diagnostic entity (126 cases, 31.0%). This reflected the high prevalence of systemic lupus erythematosus (SLE) patients in Malaysia. The most common histological pattern of lupus nephritis was diffuse proliferative glomerulonephritis: WHO Class IV (96 cases, 76.2%). Other diagnostic entities were minimal change disease (28.5%), proliferative glomerulonephritis (10.6%), IgA nephropathy (9.8%), focal glomerulosclerosis (4.9%), membranous glomerulonephritis (4.4%), transplant rejection (3.9%), end stage nephropathy (3.4%) and others (3.4%). The morphological pattern of renal biopsies in Johor was similar to that reported in the University Hospital Kuala Lumpur.

Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

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Zahra Habibagahi

2015-07-01

Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.

Treatment of Cutaneous Lupus Erythematosus

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Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

Renal damage after extracorporeal shock-wave lithotripsy detected by magnetic resonance imaging

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Torii, Shinichiro; Machida, Toyohei; Ooishi, Yukihiko; Tashiro, Kazuya; Mochizuki, Atsushi; Yoshigoe, Fukuo

1988-08-01

The acute effects of extracorporeal Shock-wave lithotripsy (ESWL) on morphology of the renal parenchyma were evaluated by Magnetic Resonance Imaging (MRI) in 15 kidneys, before and immediately after (within 24 hours) ESWL in 11 cases. The renal parenchymal damages were observed by MRI as the changes of signal itensity of renal cortex and medulla, perirenal fluid, loss of corticomedullar differentiation, and other renal traumas. Loss of corticomedullar differentiation was seen in 9/11 cases and peripheral fluid of the kidney was seen in 4/11 cases. Irregular and edematous changes of renal capsula were seen in 5/11 cases. Obvious abnormal findings indicated renal trauma were not observed in this study. Several MRI findings may transient and reversible changes and the morpholigic changes detected by MRI may attributed to renal parenchymal obstruction and edema and decreasing of renal capillary flow, such as in renal contusion. It is concluded that MRI is very sensitive and the best technique to detect the effects and clinical trouble of ESWL.

Renal damage induced by dosorubicin-lipiodol emulsion infused into rabbit renal artery : comparison with CT and histologic findings

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Kim, Jin Gyoo; Moon, Tae Young; Lee, Suck Hong; Kim, Byung Soo; Choi, Sang Yul; Park, Choong Hoon

1998-01-01

The purpose of this study is to evaluate the utility of renal CT scanning and to histologically correlate renal damage induced by renal arterial infusion of 0.2 ml/kg of doxorubicin-lipiodol emulsion. Renal CT scans of 20 rabbit kidneys were obtained 15 days after transcatheter arterial chemoembolization and were classified into four grades, as follows: grade 0 - no fleck, grade 1 - one to three nodular flecks; grade 2 - four or more nodular flecks, or one semilunar fleck; and grade 3 - two or more semilunar flecks. The percentage of histological section occupied by lesion was determined using squared paper, and compared with the grades determined on the basis of CT. The histologic findings were interstitial inflammatory cell infiltration, intratubular lipiodol droplets, dystrophic calcification, and and cellular necrosis. The mean sizes of grade 0, 1, 2 and 3 histological lesions were 2.2 % (n=5), 4.5 % (n=4), 21.9 % (n=7), and 24% (n=4), respectively. Grades 0 and 1 accounted for nine cases (3.2%), while grades 2 and 3 accounted for 11 (22.6%); this difference was statistically significant (p<0.01). CT findings showing nodular or semilunar flecks 15 days after infusion into the renal artery of doxorubicin-lipiodol emulsion correlate with the size of the damaged kidney, as seen on histological specimens. (author). 19 refs., 3 tabs., 5 figs

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study

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Fabiola Reyes-Martínez

2018-03-01

Full Text Available Objectives: Urinary levels of TWEAK (uTWEAK may be correlated with the degree of lupus nephritis (LN activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. Methods: An exploratory study was performed; four groups of patients were analyzed as follows: 1 patients with systemic lupus erythematosus (SLE without renal activity (SLE-LN, 2 patients with SLE with renal activity (SLE + LN, 3 patients with other types of glomerulopathy (glomerulonephritis, GMN, 4 and healthy patients (controls. Results: In all, 44 patients, with an average age of 35.9 ± 11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE + LN compared with patients in the other groups: SLE + LN 12.88 ± 8.33, SLE-LN 3.12 ± 2.31, GMN 4.36 ± 2.31 and controls 2.41 ± 1.94 pg/mg Cr (p = 0.007. A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC curve analysis revealed that uTWEAK levels above 4.91 pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75–0.99. However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. Conclusions: Our study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy. Resumen: Objetivos: Los niveles urinarios de TWEAK (uTWEAK pueden correlacionarse con el grado de actividad de nefritis lúpica (NL. Nuestro objetivo fue determinar la sensibilidad y especificidad de los uTWEAK en pacientes mexicanos con NL activa sin

Autoantibodies in renal diseases – clinical significance and recent developments in serological detection

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Gianna eKirsztajn

2015-05-01

Full Text Available Autoimmune dysfunctions are the bête noire in a range of debilitating nephropathies. Autoimmune-mediated damage to the kidneys can be triggered by autoantibodies directed against specific proteins or renal structures, for example the phospholipase A2 receptor or the glomerular basement membrane, resulting in glomerular diseases such as primary membranous nephropathy or Goodpasture’s disease. Moreover, secondary damage to the kidney can be part of the wide-reaching effects of systemic autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE – the latter counts lupus nephritis among its most severe manifestations. Systemic autoimmune diseases are characterized by non-organ-specific autoantibodies, directed for example against neutrophil cytoplasmic antigens in systemic vasculitis and against double-stranded DNA and nucleosomes in SLE.A large variety of innovative and highly specific and sensitive autoantibody tests have been developed in the last years that are available to identify autoimmune kidney diseases at an early stage. Thus, serological in vitro diagnostics allow for appropriate interventional therapy in order to prevent disease progression often resulting in need of dialysis and transplantation.

The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury.

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Jaklien C Leemans

Full Text Available Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2 is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/- or TLR2(+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/- mice compared with TLR2(+/+ animals. Although, the obstructed kidneys of TLR2(-/- mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.

Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

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Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D

2017-11-01

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy

Renal Localization of 67Ga Citrate in Noninfectious Nephritis

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Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu

1992-01-01

67 Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of 67 Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal 67 Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of 67 Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher 67 Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal 67 Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal 67 Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, 67 Ga citrate scan is useful in predicting renal involvement.

Effect of Hydroalcholic Extract of Curcuma longa on Adriamycin-Induced Renal Damage in Rats

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R. Mohebbati; A.A. Abbasnezhad; A. Khajavi Rad; M. Haghshenas; M.R. Khazdeir

2016-01-01

Aims: Adriamycin is one of the anti-cancer medications. Nevertheless, the medication causes renal damage. Curcuma longa has anti-inflammatory and anti-oxidant effects. The aim of this study was to determine the effects of hydroalcoholic extract of Curcuma longa on renal damage due to Adriamycin in the rat. Materials & Methods: In the experimental study, 32 male Wistar rats were studied. Via simple random method, the rats were divided into four groups including control, Adriamycin (5mg/Kg)...

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

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Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Atherosclerotic vessel damage in systemic lupus erythematosus and antiphospholipid syndrome in men

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A. I. Iljina

2005-01-01

Full Text Available Objective. To study prevalence of clinical and subclinical atherosclerosis signs in men with systemic lupus erythematosus (SLE and antiphospholipid syndrome, to assess relationship between atherosclerotic vessel damage, risk factors, CRP and anti-cardiolipin antibodies (АСА Material and methods. 62 pts were included. Mean age was 35,7+11,6 years, mean disease duration - 129,3± 102 months. Traditional and related to the disease risk factors were analyzed. To reveal atherosclerotic vessel damage carotid sonographic examination was performed. Serum CRP concentration was evaluated by high sensitivity nephelometric immunoassay. IgG and IgM АСА were assessed by solid-phase immuno-enzyme assay. Results. Sonographic signs of carotid damage was revealed in 58% of pts, clinical signs of atherosclerosis - in 42%. Pts were divided into two groups according to intima-media complex thickness (IMCT. Group I included 36 pts with atherosclerotic vessel damage signs (IMCT?0,9 mm. Group 2-26 pts with IMCT<0,9 mm. Mean age at the examination, age of disease onset, disease duration, smoking frequency damage index in group I pts were higher than in group 2 pts. Mean CRP concentration in atherosclerosis group was significantly higher than in group 2 (p=0,007. 19 pts had APS signs. 43 pts did not. CRP level significantly correlated with IMCT in SLE pts with and without APS (p<0,05. Pts with atherosclerosis had higher IgG АСА level though the differences were not statistically significant. Conclusion. Men with SLE with or without APS have high risk of atherosclerosis development. CRP elevation is associated with IMCT increase.

Renal damage after extracorporeal shock-wave lithotripsy detected by magnetic resonance imaging

International Nuclear Information System (INIS)

Torii, Shinichiro; Machida, Toyohei; Ooishi, Yukihiko; Tashiro, Kazuya; Mochizuki, Atsushi; Yoshigoe, Fukuo

1988-01-01

The acute effects of extracorporeal Shock-wave lithotripsy (ESWL) on morphology of the renal parenchyma were evaluated by Magnetic Resonance Imaging (MRI) in 15 kidneys, before and immediately after (within 24 hours) ESWL in 11 cases. The renal parenchymal damages were observed by MRI as the changes of signal itensity of renal cortex and medulla, perirenal fluid, loss of corticomedullar differentiation, and other renal traumas. Loss of corticomedullar differentiation was seen in 9/11 cases and peripheral fluid of the kidney was seen in 4/11 cases. Irregular and edematous changes of renal capsula were seen in 5/11 cases. Obvious abnormal findings indicated renal trauma were not observed in this study. Several MRI findings may transient and reversible changes and the morpholigic changes detected by MRI may attributed to renal parenchymal obstruction and edema and decreasing of renal capillary flow, such as in renal contusion. It is concluded that MRI is very sensitive and the best technique to detect the effects and clinical trouble of ESWL. (author)

Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

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Sato, J O; Corrente, J E; Saad-Magalhães, C

2016-11-01

Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p  0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

Economic evaluation of lupus nephritis in the Systemic Lupus International Collaborating Clinics inception cohort using a multistate model approach.

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Barber, Megan R W; Hanly, John G; Su, Li; Urowitz, Murray B; Pierre, Yvan St; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Wallace, Daniel J; Isenberg, David A; Rahman, Anisur; Ginzler, Ellen M; Petri, Michelle; Bruce, Ian N; Fortin, Paul R; Gladman, Dafna D; Sanchez-Guerrero, Jorge; Ramsey-Goldman, Rosalind; Khamashta, Munther A; Aranow, Cynthia; Mackay, Meggan; Alarcón, Graciela S; Manzi, Susan; Nived, Ola; Jönsen, Andreas; Zoma, Asad A; van Vollenhoven, Ronald F; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Sam Lim, S; Kalunian, Kenneth C; Inanc, Murat; Kamen, Diane L; Peschken, Christine A; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Farewell, Vernon; Clarke, Ann E

2017-11-28

Little is known about the long-term costs of lupus nephritis (LN). These were compared between patients with and without LN based on multistate modelling. Patients from 32 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using estimated glomerular filtration rate (eGFR) or proteinuria (ePrU). A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. 1,545 patients participated, 89.3% female, mean age at diagnosis 35.2 years (SD 13.4), 49.0% Caucasian, and mean follow up 6.3 years (SD 3.3). LN developed in 39.4% by the end of follow up. Ten-year cumulative costs were greater in those with LN and an eGFR 60 ml/min) or with LN and ePrU > 3 g/d ($84 040 versus $20 499 if no LN and ePrU < 0.25 g/d). Patients with eGFR < 30 ml/min incurred 10-year costs 15-fold higher than those with normal eGFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future healthcare costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The protective effects of tadalafil on renal damage following ischemia reperfusion injury in rats

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Bulent Erol

2015-09-01

Full Text Available Ischemia-reperfusion injury can cause renal damage, and phosphodiesterase inhibitors are reported to regulate antioxidant activity. We investigated the prevention of renal damage using tadalafil after renal ischemia reperfusion (I/R injury in rats. A total of 21 adult male Wistar albino rats were randomly divided into three groups of seven, including Group 1-control, Group 2-I/R, and Group 3-tadalafil + I/R group (I/R-T group received tadalafil intraperitoneally at 30 minutes before ischemia. Inducible nitric oxide synthase, endothelial nitric oxide synthase, malondialdehyde, and total antioxidant capacity levels were evaluated, and histopathological changes and apoptosis in the groups were examined. Tadalafil decreased malondialdehyde levels in the I/R group and increased the total antioxidant capacity level. Histopathological and immunohistochemical findings revealed that tadalafil decreased renal injury scores and the ratios of injured cells, as measured through apoptotic protease activating factor 1, inducible nitric oxide synthase, and endothelial nitric oxide synthase levels. We suggest that tadalafil has protective effects against I/R-related renal tissue injury.

Renal Localization of {sup 67}Ga Citrate in Noninfectious Nephritis

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Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu [Chungnam University College of Medicine, Deajeon (Korea, Republic of)

1992-07-15

{sup 67}Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of {sup 67}Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal {sup 67}Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of {sup 67}Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher {sup 67}Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal {sup 67}Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal {sup 67}Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, {sup 67}Ga citrate scan is useful in predicting renal involvement.

Renal damage mediated by oxidative stress: a hypothesis of protective effects of red wine.

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Rodrigo, Ramón; Rivera, Gonzalo

2002-08-01

Over the last decade, oxidative stress has been implicated in the pathogenesis of a wide variety of seemingly unrelated renal diseases. Epidemiological studies have documented an association of moderate wine consumption with a decreased risk of cardiovascular and neurological diseases; however, similar studies in the kidney are still lacking. The kidney is an organ highly vulnerable to damage caused by reactive oxygen species (ROS), likely due to the abundance of polyunsaturated fatty acids in the composition of renal lipids. ROS are involved in the pathogenic mechanism of conditions such as glomerulosclerosis and tubulointerstitial fibrosis. The health benefits of moderate consumption of red wine can be partly attributed to its antioxidant properties. Indeed, the kidney antioxidant defense system is enhanced after chronic exposure to moderate amounts of wine, a response arising from the combined effects of ethanol and the nonalcoholic components, mainly polyphenols. Polyphenols behave as potent ROS scavengers and metal chelators; ethanol, in turn, modulates the activity of antioxidant enzymes. Therefore, a hypothesis that red wine causes a decreased vulnerability of the kidney to the oxidative challenges could be proposed. This view is partly supported by direct evidences indicating that wine and antioxidants isolated from red wine, as well as other antioxidants, significantly attenuate or prevent the oxidative damage to the kidney. The present hypothesis paper provides a collective body of evidence suggesting a protective role of moderate wine consumption against the production and progression of renal diseases, based on the existing concepts on the pathophysiology of kidney injury mediated by oxidative stress.

Mizoribine: A New Approach in the Treatment of Renal Disease

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Yukihiko Kawasaki

2009-01-01

Full Text Available Mizoribine (MZB is an imidazole nucleoside and an immunosuppressive agent. The immunosuppressive effect of MZB has been reported to be due to the inhibition of DNA synthesis in the S phase of the cell cycle. Because of its relative lack of toxicity, during the past decade MZB has been frequently used instead of azathioprine as a component of immunosuppressive drug regimens. MZB is being used to treat renal transplantation patients, IgA nephropathy, lupus erythematosus, and childhood nephrotic syndrome (NS, and some recent studies have assessed the efficacy of oral MZB pulse therapy for severe lupus nephritis, steroid-resistant NS, and frequently relapsing-steroid-dependent NS. This review summarizes the published findings on the efficacy of MZB for renal disease including IgA nephropathy, lupus nephritis, and NS, as well as of oral MZB pulse therapy for severe lupus nephritis and NS, and also the mechanism of the effect of oral MZB pulse therapy on the lymphocyte cell cycle.

T cell-derived IFN-γ downregulates protective group 2 innate lymphoid cells in murine lupus erythematosus.

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Düster, Mathis; Becker, Martina; Gnirck, Ann-Christin; Wunderlich, Malte; Panzer, Ulf; Turner, Jan-Eric

2018-04-19

Innate lymphoid cells (ILCs) are important regulators of the immune response and play a crucial role in the restoration of tissue homeostasis after injury. GATA-3 + IL-13- and IL-5-producing group 2 innate lymphoid cells (ILC2s) have been shown to promote tissue repair in barrier organs, but despite extensive research on ILCs in the recent years, their potential role in autoimmune diseases is still incompletely understood. In the present study, we investigate the role of ILC2s in the MRL/MpJ-Fas lpr (MRL-lpr) mouse model for severe organ manifestation of systemic lupus erythematosus (SLE). We show that in these MRL-lpr mice, progression of lupus nephritis is accompanied with a reduction of ILC2 abundance in the inflamed renal tissue. Proliferation/survival and cytokine production of kidney-residing ILC2s was suppressed by IFN-γ and, to a lesser extent, by IL-27 which were produced by activated T cells and myeloid cells in the nephritic kidney, respectively. Most importantly, restoration of ILC2 numbers by IL-33-mediated expansion ameliorated lupus nephritis and prevented mortality in MRL-lpr mice. In summary, we show here that development of SLE-like kidney inflammation leads to a downregulation of the renal ILC2 response and identify an ILC2-expanding therapy as a promising treatment approach for autoimmune diseases. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PP144. Profile of lupus pregnancy in internal medecine practice.

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Haddad, T; Hakem, D; Berrah, A

2012-07-01

The pregnancies in systemic erythematous lupus (SLE) disease is a situation of high risk and involve both the mother and the fetus. The prematurity and the miscarriage are there more frequent, with increase risks of eclampsia, acute hypertension, HELP syndrome and of worsening renal disease. So the morbimortality is multiplied particularly when a anti-phospholipid syndrome 'APLS' is associated. The pregnancy remains however authorized when the SLE is in remission for more than 6 months with a validated treatment and successful means of monitoring. To review the clinical profile of the pregnancies at the SLE patients with or without APLS in Internal Medicine Practice. it's a retrospective study, in an internal medical centre over a period going from January, 2008 till December, 2011. The collection of the data is made from the index cards of clinical observations collecting items to interpret the data. All the patients are diagnosed referring to the criteria ACR (SLE/APLS) and all benefit from a follow-up in a obstetrics monitoring (ultrasounds to monitor growth and placental development). On a cohort of 80 SLE young patients hospitalized we brought together 20 patients answering eligibility criteria. The average age is of 26 years (21-41), SLE evolve with an average of 2.5years, the parity is estimated at 5 on average by patient. The pregnancies are programmed in only in 25% . The others cases of pregnancy remain the consequence of a not adapted contraception (50%). Lupus patients have history of renal damage (8) requiring immunosuppressive therapy (4) but renal function is preserved at all the patient's. The treatment is adapted to the clinical context and prophylactic doses of heparin and a baby aspirin are required in most situations. The cardiovascular and metabolic risk factors show an overweight (12), one dyslipemia (10), type 2 diabetes (2), and hypertension (3). The pregnancy is at the origin of a degradation of the renal function (4) with definitive

The involvement of galectin-3 in skin injury in systemic lupus erythematosus patients.

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Shi, Z; Meng, Z; Han, Y; Cao, C; Tan, G; Wang, L

2018-04-01

Objective Our previous research suggested that anti-galectin-3 antibody was highly associated with the development of lupus skin lesions in systemic lupus erythematosus (SLE). In this study we aimed to investigate the involvement of galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy controls. Galectin-3 was examined by ELISA and immunohistochemical staining in serum and skin, respectively. Results Serum galectin-3 was significantly higher in patients with SLE than in those with dermatomyositis ( P  0.05). As for subtypes of skin lesions in SLE, galectin-3 expression was lower in chronic cutaneous lupus erythematosus than in acute cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is unlikely to play a role in the pathogenesis of lupus skin damage, but can be a potential biomarker for the measurement of SLE disease activity. Galectin-3 is greatly reduced in patients with lupus lesions compared with healthy controls, which may contribute to the recruitment of inflammatory cells in the skin.

Renal involvement in the antiphospholipid syndrome (APS)-APS nephropathy.

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Tektonidou, Maria G

2009-06-01

Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

Dyslipidemia in systemic lupus erythematosus: just another comorbidity?

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Tselios, Konstantinos; Koumaras, Charalambos; Gladman, Dafna D; Urowitz, Murray B

2016-04-01

Among traditional atherosclerotic risk factors, dyslipidemia is believed to decisively affect the long-term prognosis of lupus patients, not only with regard to cardiovascular events but also by influencing other manifestations, such as lupus nephritis. The aim of this study was to review the epidemiology, pathogenesis, evidence for its impact on atherosclerosis manifestations and management of dyslipidemia in lupus patients. English-restricted MEDLINE database search (Medical Subject Headings: lupus or systemic lupus erythematosus and dyslipidemia or hyperlipidemia). The prevalence of dyslipidemia in systemic lupus erythematosus (SLE) ranges from 36% at diagnosis to 60% or even higher after 3 years, depending on definition. Multiple pathogenetic mechanisms are implicated, including antibodies against lipoprotein lipase and cytokines affecting the balance between pro- and anti-atherogenic lipoproteins. Dyslipidemia has a clear impact on clinical cardiovascular disease and surrogate markers for subclinical atherosclerosis. Moreover, it negatively affects end-organ damage (kidneys and brain). Treatment with statins yielded contradictory results as per minimizing cardiovascular risk. Dyslipidemia is a significant comorbidity of lupus patients with multiple negative effects in the long term. Its treatment represents a modifiable risk factor; prompt and adequate treatment can minimize unnecessary burden in lupus patients, thus reducing hospitalizations and their overall morbidity and mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

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McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P. J.

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials. PMID:29928273

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

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McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Case Report: An atypical case of systemic lupus erythematosus ...

African Journals Online (AJOL)

Background: Systemic lupus erythematosus (SLE) is a multisystem disease that can be a diagnostic conundrum. Case report: We describe a patient who presented with recurrent fleeting exudative and hemorrhagic pleural effusion. It took multiple visits over 3 months and renal biopsy to con rm the diagnosis of SLE.

Computerized tomography data on CNS affection in systemic lupus erythematosus

International Nuclear Information System (INIS)

Ivanova, M.M.; Bliznyuk, O.I.; Todua, F.I.; Tumanova, A.A.

1989-01-01

Computed tomography (CT) of the brain was employed in 40 patients with systemic lupus erythematosus (SLE). Clinical cerebral pathology was obvious in 30 and absent in 10 patients. By CT cerebral symptoms were divided of 4 groups. Clinical symptom complexes of CNS defects and SLE were reflected on definite CT images correlated with focal damage to the brain. CT picture of enlarged subarachnoid space, ventricles and basal cisterns can be observed in SLE patients without neurological symptoms. This indicated likely subclinical cerebral affection

Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management.

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Lam, Nguyet-Cam Vu; Ghetu, Maria V; Bieniek, Marzena L

2016-08-15

Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services.

Effects of renal denervation on end organ damage in hypertensive patients

NARCIS (Netherlands)

Verloop, WL; Vink, Eva E.; Spiering, Wilko; Blankestijn, PJ; Doevendans, Pieter A.; Bots, Michiel L.; Vonken, EPA; Voskuil, Michiel; Leiner, Tim

Background: Renal denervation (RDN) is believed to reduce sympathetic nerve activity and is a potential treatment for resistant hypertension. The present study investigated the effects of RDN on end organ damage (EOD). Design: The present study was a prospective cohort study (registered as

Mood Disorders in Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Hanly, John G; Su, Li; Urowitz, Murray B

2015-01-01

OBJECTIVE: To examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE). METHODS: Patients were assessed annually for mood...... disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College...... was associated with Asian race/ethnicity (P = 0.01) and treatment with immunosuppressive drugs (P = 0.003). Mood disorders were associated with lower mental health and mental component summary scores but not with the SLEDAI-2K, SDI, or lupus autoantibodies. Among the 232 patients with depression, 168 (72...

The Steroids in the Maintenance of Remission of Proliferative Lupus Nephritis (SIMPL Pilot Trial

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Lauren Galbraith

2014-11-01

Full Text Available Background: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. Objectives: We undertook a pilot RCT to determine the feasibility of a larger trial. Design: Pilot randomized controlled trial. Setting: Single center Canadian outpatient nephrology clinic. Patients: Participants with systemic lupus erythematosus (SLE and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. Measurements: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. Methods: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation compared to a matching placebo (withdrawal. Results: Of nineteen eligible patients screened, 15 (79% were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50% patients in the continuation group (three renal and one major non-renal flare, compared with one patient (14% in the withdrawal group (one renal flare. Three participants (38% in the continuation group had minor flares, while no patients in the withdrawal group did. Limitations: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. Conclusions: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. Trial registration: Current Controlled Trials ISRCTN31327267.

Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report.

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Deng, Datong; Sun, Li; Xia, Tongjia; Xu, Min; Wang, Youmin; Zhang, Qiu

2016-07-01

A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.

Lupus

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What is lupus? Lupus is an autoimmune disease. This means that your immune system attacks healthy cells and tissues by mistake. This can ... vessels, and brain. There are several kinds of lupus Systemic lupus erythematosus (SLE) is the most common ...

Associated Variables of Myositis in Systemic Lupus Erythematosus: A Cross-Sectional Study.

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Liang, Yan; Leng, Rui-Xue; Pan, Hai-Feng; Ye, Dong-Qing

2017-05-26

BACKGROUND This study aimed to estimate the point prevalence of myositis and identify associated variables of myositis in systemic lupus erythematosus (SLE). MATERIAL AND METHODS Clinical date of patients hospitalized with lupus at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital were collected. Patients were defined as having myositis if they reported the presence of persistent invalidating muscular weakness combined with increased levels of creatine phosphokinase (CPK) and abnormal electromyography (EMG). RESULTS The study sample comprised 1701 lupus patients, of which 44 had myositis. Patients with SLE-associated myositis are more likely to have skin rash, alopecia, pericarditis, vasculitis, anti-Sm, anti-RNP, anti-dsDNA, thrombocytopenia, leukopenia, low C3, low C4, high erythrocyte sedimentation rate (ESR), high D-dimer, and active disease. Multivariate logistic regression found positive associations between leukopenia, alopecia, and active disease with myositis. Negative associations between myositis with the use of corticosteroids or immunosuppressive drugs were revealed in univariate and multivariate analysis. CONCLUSIONS The point prevalence of myositis was 2.6% in SLE patients. The significant association of alopecia, leukopenia, and active disease with myositis suggests that organ damage, hematological abnormality, and high disease activity promote the progression of myositis in lupus patients.

Pediatric Systemic Lupus Erythematosus: Learning From Longer Follow Up to Adulthood

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Giorgio Costagliola

2018-05-01

Full Text Available Background: Pediatric systemic lupus erythematosus (pSLE is a rare condition, representing approximately 10% of SLE cases. The aim of this study was to identify variables to improve the diagnostic awareness and management of pSLE patients.Methods: This retrospective study included 25 patients diagnosed with pSLE and followed at the University of Pisa. We collected data about clinical profile at disease onset and during a long-term follow-up, including disease activity, organ damage development, and treatments received.Results: The mean patient age at disease onset was 14.6 ± 1.6 years, and the mean follow-up period was 14.17 ± 8.04 years. The most common initial manifestations were arthritis, malar rash, and cytopenias. The median time to diagnosis since the first symptoms was 6 months, and was significantly longer in patients with hematological onset (54 months. During follow-up, the number of patients with renal involvement showed a significant increase, from 36% at diagnosis to 72.2% after 10 years of disease evolution. Patients who developed chronic organ damage maintained a higher time-averaged disease activity during follow-up and received a significantly higher dose of corticosteroids.Conclusion: Patients with immune cytopenia represent a group deserving strict clinical follow-up for the risk of evolution to SLE. Intense surveillance of renal function, early treatment and steroid-sparing strategies should be strongly considered in the management of pSLE patients.

Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.

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Artim-Esen, Bahar; Çene, Erhan; Şahinkaya, Yasemin; Ertan, Semra; Pehlivan, Özlem; Kamali, Sevil; Gül, Ahmet; Öcal, Lale; Aral, Orhan; Inanç, Murat

2014-07-01

Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

Neuraminidase activity mediates IL-6 production by activated lupus-prone mesangial cells.

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Sundararaj, Kamala; Rodgers, Jessalyn I; Marimuthu, Subathra; Siskind, Leah J; Bruner, Evelyn; Nowling, Tamara K

2018-04-01

The development of nephritis is a leading cause of morbidity and mortality in lupus patients. Although the general pathophysiological progression of lupus nephritis is known, the molecular mediators and mechanisms are incompletely understood. Previously, we demonstrated that the glycosphingolipid (GSL) catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU) and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly increased. To better understand the role and mechanisms by which this pathway contributes to the progression of LN, we analyzed the expression and effects of NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1 expression, NEU activity, and IL-6 production are significantly increased in stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL-6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and in renal sections from nephritic MRL/lpr mice. Together, our results suggest that NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG-receptor complex signaling pathway.

Mecanismos del daño celular en la insuficiencia renal aguda Mechanisms of cell damage in acute renal failure

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José Martínez

1989-01-01

Full Text Available

Los mecanismos del da no celular en la insuficiencia renal aguda Incluyen alteraciones en la producción de energía, la permeabilidad celular y el transporte de calcio. Dichas alteraciones producen cambios progresivos en la estructura celular que pueden ser reversibles si desaparece la causa que llevó a la falla renal, excepto cuando se alcanza la fase final de la lesión de la membrana y se llega a necrosis celular. Este mismo fenómeno probablemente ocurre tambIén en situaciones clínicas.

The mechanisms of cellular damage In acute renal failure Include alterations In energy production, cell membrane permeability and calcium transport. These changes lead to progressive damage of the whole cellular structure which In general can be reversible If the precipitating cause disappears, except when the final stages of cell membrane lesion take place and cellular necrosis has occurred. This phenomenon probably applies for the clinical settling as well.

Diabetes insipidus-like state complicating percutaneous transluminal renal stenting for transplant renal artery stenosis.

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Tian, Lu; He, Yangyan; Zhang, Hongkun; Wu, Ziheng; Li, Donglin; Chen, Shanwen

2014-07-01

To report the incidence, etiology, and treatments of diabetes insipidus-like state that complicate percutaneous transluminal renal stenting (PTRS) for transplant renal artery stenosis (TRAS). Data from 7 patients on whom PTRS for TRAS was performed between October 2008 and March 2012 were reviewed retrospectively. The parameters investigated included blood flow velocity, blood pressure, and creatinine levels before and after the intervention. The procedural success rate was 100%. Three cases developed a diabetes insipidus-like state in the immediate postprocedural period. Urine output returned to normal within 2 weeks after treatment. The median blood flow velocity was significantly reduced from 4.51 m/sec (4.31-4.61 m/sec) at the time of TRAS diagnosis to 1.33 m/sec (1.31-1.51 m/sec) at the most recent follow-up of the group with a diabetes insipidus-like state. The ratio of median blood flow velocity before and after stenting in the group with a diabetes insipidus-like state was significantly higher than that in the group without a diabetes insipidus-like state (3.39 vs. 1.93). Diabetes insipidus-like state that complicates PTRS for TRAS is not an uncommon event, but appears to be underreported in the medical literature. A high ratio of pre- and poststenting median blood flow velocity may be a predictor for a postprocedural diabetes insipidus-like state. The most probable cause may be the marked increase in renal arterial flow. Early recognition of the condition is essential to avoid dehydration and electrolyte imbalance. Copyright © 2014 Elsevier Inc. All rights reserved.

Kallikrein-like amidase activity in renal ischemia and reperfusion

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M.D. Carattino

2000-05-01

Full Text Available We assessed a kallikrein-like amidase activity probably related to the kallikrein-kinin system, as well as the participation of leukocyte infiltration in renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min of ischemia and to different periods of reperfusion. A control group consisted of sham-operated mice, under similar conditions, except for ischemia induction. Kallikrein-like amidase activity, Evans blue extravasation and myeloperoxidase activity were measured in kidney homogenates, previously perfused with 0.9% NaCl. Plasma creatinine concentration increased only in the 60-min ischemic group. After 20 min of ischemia and 1 or 24 h of reperfusion, no change in kallikrein-like amidase activity or Evans blue extravasation was observed. In the mice subjected to 20 min of ischemia, edema was evident at 1 h of reperfusion, but kidney water content returned to basal levels after 24 h of reperfusion. In the 60-min ischemic group, kallikrein-like amidase activity and Evans blue extravasation showed a similar significant increase along reperfusion time. Kallikrein-like amidase activity increased from 4 nmol PNA mg protein-1 min-1 in the basal condition to 15 nmol PNA mg protein-1 min-1 at 10 h of reperfusion. For dye extravasation the concentration measured was near 200 µg of Evans blue/g dry tissue in the basal condition and 1750 µg of Evans blue/g dry tissue at 10 h of reperfusion. No variation could be detected in the control group. A significant increase from 5 to 40 units of DAbs 655 nm g wet tissue-1 min-1 in the activity of the enzyme myeloperoxidase was observed in the 60-min ischemic group, when it was evaluated after 24 h of reperfusion. Histological analysis of the kidneys showed migration of polymorphonuclear leukocytes from the vascular bed to the interstitial tissue in the 60-min ischemic group after 24 h of reperfusion. We conclude that the duration of ischemia is critical for the development of damage

Pulse cyclophospamide in severe lupus nephritis: Southern Indian experience

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Das Uttara

2010-01-01

Full Text Available To evaluate the efficacy and safety of the monthly pulse IV cyclophosphamide (IVC therapy in patients with severe lupus nephritis, we studied 39 patients of lupus nephritis on IVC therapy between 1998 to 2002. Single monthly cyclophosphamide (0.75-1 g/m² was infused intravenously with oral prednisolone (0.5 mg/kg per day and appropriate hydration. Of the 39 pa-tients 25 (86.2% patients were females and 4 (13.8% were males. Six (2% cases had irregular follow-up and 3 patients had expired during the initial cycles and were excluded from the study. The mean age was 25.6 + 6.72 years (range 10-40 years. The mean duration of the disease from the onset to renal biopsy was 24.2 + 18.5 months. The clinical presentations included nephrotic syndrome (34.5%, acute glomerulonephritis (31.0%, Pyrexia of unknown origin (PUO (10.3%, and rapidly progressive renal failure (6.7%. Renal insufficiency was present in 47.2% cases. Twenty-two (75.9% patients had diffuse proliferative glomerulonephritis (class IV, 6 (20.7% focal proliferative glomerulonephritis (class III, and one (3.4% class Vd. After a mean follow-up of 15.8 months, out of 29 patients, 13 (44.8% had achieved complete remission, 7 (24.1% partial remission and 9 (31.0% cases did not respond to the therapy. Side effects of the therapy included vomiting and nausea (100% and hair loss during the first few doses of IVC. In addition, one case had dysfunctional uterine bleeding and two patients had avascular necrosis of femoral head. We conclude that our data indicate that IVC in severe lupus nephritis is effective in Indian patients though longer follow-up is required.

Crusted scabies in a chid with systemic lupus erythematosus

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Nurimar C.F. Wanke

1992-03-01

Full Text Available A child with systemic lupus erythematosus who has been treated with prednisone for three years, developed crusted scabies. Scrapings from lesions revealed Sarcoptes scabiei adult mites mad eggs. The patient died with septicemia and renal failure soon after starting topical 20% sulfur. A marked improvement was observed in the cutaneous lesions.

The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.

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Kamiyama, Yoshihiro; Yamashita, Shinichi; Nakagawa, Atsuhiro; Fujii, Shinji; Mitsuzuka, Koji; Kaiho, Yasuhiro; Ito, Akihiro; Abe, Takaaki; Tominaga, Teiji; Arai, Yoichi

2017-09-01

In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.

Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model.

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Flávio Teles

Full Text Available The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP, in the 5/6 renal ablation model (Nx. Adult male Wistar rats underwent Nx and were divided into untreated (Nx and RP-treated (Nx+RP groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes.

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Piantoni, S; Regola, F; Zanola, A; Andreoli, L; Dall'Ara, F; Tincani, A; Airo', P

2018-01-01

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons ( p adj ). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls ( p = .04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K ≥ 6 ( n = 13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype ( p adj  = .005) as well as those with an effector memory ( p adj  = .004) and TDEM ( p adj  = .002) phenotype and a trend of decrease of regulatory T-cells (TREGs) ( p = .02), in comparison with patients with low disease activity ( n = 38). Patients with damage (SDI ≥ 1) tended to show an expansion of TDEM among CD4+ T-cells as compared with

Epidemiology and survival of systemic lupus erythematosus in Hong Kong Chinese.

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Mok, C C

2011-06-01

Systemic lupus erythematosus (SLE) is a fairly common rheumatic disease in Hong Kong, China. The prevalence and annual incidence of SLE are estimated to be 0.1% and 6.7/100,000 population, respectively. The 10-year cumulative survival of SLE patients in Hong Kong is 83% and the age and gender-adjusted standardized mortality ratio was 5.25 (1.64-10.4) from 1999 to 2008. The commonest cause of death is infections (60%), followed by cardiovascular complications (16%). Life expectancy analysis reveals a loss of 20 years in women and 27 years in men when SLE develops at birth. The loss in life years is greatest in the younger age groups. Renal damage is the most frequent disease-related damage, whereas musculoskeletal damage is the commonest treatment-related complication. The quality of life of our SLE patients is impaired and declines over time, which is contributed by new organ damage. One-third of our patients lose their ability to work within 5 years of disease onset, which is mainly attributed to musculoskeletal pain, fatigue, anxiety and depression symptoms, and memory deterioration. With the availability of novel therapeutics and an increased awareness of complication prevention in SLE, it is expected that our patients will live longer with a better quality of life in the next decade.

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

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Rodrigo C. Oliveira

2015-01-01

Full Text Available We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA. Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

Sodium intake modifies the negative prognostic value of renal damage prior to treatment with ACE inhibitors on proteinuria induced by adriamycin

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Kramer, Andrea B.; Bos, Hendrik; van Goor, Harry; Navis, Gerjan J.

2006-01-01

Background: Antiproteinuric treatment by ACE inhibition (ACEi) provides renoprotection. However, resistance to antiproteinuric intervention occurs frequently, resulting in progressive renal damage. The extent of renal damage prior to treatment with ACEi reversely correlates with the antiproteinuric

ِAssessment of lupus nephritis by measuring urinary retinol binding ...

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Ehab

Background: Renal disease is a common manifestation of systemic lupus erythematosus (SLE). Both glomerular and ... Objective: The study was aimed to assess the urinary RPB level in SLE patients with and without evidence of .... Twenty-one patients were receiving prednisone (1-2 mg/Kg/day) either alone (n= 13) or.

Prognostic significance of repeat biopsy in lupus nephritis: Histopathologic worsening and a short time between biopsies is associated with significantly increased risk for end stage renal disease and death.

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Arriens, Cristina; Chen, Sixia; Karp, David R; Saxena, Ramesh; Sambandam, Kamalanathan; Chakravarty, Eliza; James, Judith A; Merrill, Joan T

2017-12-01

Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial. For this reason repeat biopsies are usually not utilized unless clinical evidence of refractory or recurrent disease is already present, despite known mismatches between clinical and biopsy findings. The current study quantifies the degree to which histopathologic worsening between first and second biopsies and duration between them predicts ESRD and death. Medical records of 141 LN patients with more than one biopsy were obtained from a single large urban medical center. Cases were attained using billing codes for diagnosis and procedures from 1/1999-1/2015. Biopsy worsening was defined as unfavorable histopathologic classification transitions and/or increased chronicity; if neither were present, the patient was defined as non-worsening. We used Cox proportional hazard models to study the relationship between ESRD and survival adjusting for covariates which included age at first biopsy, gender, race, initial biopsy class, and initial induction therapy. Of 630 patients screened, 141 had more than one biopsy. Advancing chronicity was detected in 48 (34.0%) and a renal class switch to worse grade of pathology was found in 54 (38.3%). At least one of these adverse second biopsy features was reported in 79 (56.0%) patients. Five years following initial biopsy, 28 (35.4%) of those with worsening histopathology on second biopsy developed ESRD, compared to 6 (9.7%) of non-worsening patients and 10 (12.7%) of patients with worsening

Lupus mastitis - peculiar radiological and pathological features

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Wani, Abdul Majid; Hussain, Waleed Mohd; Fatani, Mohamed I; Shakour, Bothaina Abdul

2009-01-01

Lupus mastitis is a form of lupus profundus that is seen in patients with systemic lupus erythematosus. It usually presents as a swelling (or swellings) in the breasts, with or without pain. The condition is recurrent and progresses along with the underlying disease, with fat necrosis, calcification, fibrosis, scarring, and breast atrophy. Lupus mastitis is often confused with malignancy and lymphoma and, in our part of the world, with tuberculosis. Confusion is especially likely when it occurs in an unusual clinical setting. In this article, we present a case that presented with unique radiological, pathological, and clinical features. Awareness of the various manifestations of lupus mastitis is essential if unnecessary interventions such as biopsies and surgeries, and their consequences, are to be avoided

Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

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Mota, Pedro; Reddy, Venkat; Isenberg, David

2017-07-01

Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis.

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Moroni, Gabriella; Vercelloni, Paolo Gilles; Quaglini, Silvana; Gatto, Mariele; Gianfreda, Davide; Sacchi, Lucia; Raffiotta, Francesca; Zen, Margherita; Costantini, Gloria; Urban, Maria Letizia; Pieruzzi, Federico; Messa, Piergiorgio; Vaglio, Augusto; Sinico, Renato Alberto; Doria, Andrea

2018-05-05

To evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time. We studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970-1985, P2 1986-2001 and P3 2002-2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test. A progressive increase in patient age at the time of LN diagnosis (ppresentation progressively decreased (pClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Therapeutic effect of total glucosides of paeony on lupus nephritis in MRL/lpr mice].

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Ding, Zhao-Xia; Yang, Shao-Feng; Wu, Qi-Fu; Lu, Ying; Chen, Yu-Yao; Nie, Xiao-Li; Jie, Hong-Yu; Qi, Jing-Min; Wang, Fan-Sheng

2011-04-01

To observe the therapeutic effect of total glucosides of paeony (TGP) on lupus nephritis (LN) in MRL/lpr mice. MRL/lpr mice with lupus nephritis were randomized into model group and TGP group. The urinary protein content was detected using Coomassie brilliant blue, and the serum levels of IgG anti-double-stranded DNA (dsDNA) antibodies and antinuclear antibodies (ANA) were measured by enzyme-linked immunosorbent assay (ELISA). The changes in the renal pathology were examined microscopically, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. At 15 and 30 days after TGP administration, the urinary protein content in the TGP group was significantly lower than that in the model group (PTGP treatment significantly lowered the serum levels of anti-dsDNA antibodies and ANA and the weight and index of spleen (PTGP treatment, the urinary protein content and the levels of anti-dsDNA antibodies and ANA decreased significantly at 15 and 30 days after TGP administration (PTGP administration, the urinary protein content was significantly lowered in the TGP group as compared to that at 15 days (PTGP can reduce urinary protein content and serum levels of anti-dsDNA antibodies and ANA, and lessen renal pathology in MRL/lpr mice with lupus nephritis, suggesting its therapeutic effect on lupus nephritis.

Childhood lupus nephritis: 12 years of experience from a developing country's perspective.

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Samanta, Moumita; Nandi, Madhumita; Mondal, Rakesh; Hazra, Avijit; Sarkar, Sumatra; Sabui, Tapas; Kundu, Chanchal Kumar; Biswas, Arnab

2017-09-01

To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank test. The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

Profiling analysis of circulating microRNA in peripheral blood of patients with class IV lupus nephritis.

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Elkin Navarro-Quiroz

Full Text Available Renal involvement in Systemic Lupus Erythematous (SLE patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group and healthy individuals (CTL group. Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (≥2 o ≤-2 and false discovery rate (0.05. We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p. These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings

Evaluation of DMSA scintigraphy and urography in assessing both acute and permanent renal damage in children

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Stokland, E.; Jacobsson, B. [Dept. of Pediatric Radiology, Sahlgrenska Univ. Hospital, Goeteborg Univ. (Sweden).; Hellstroem, M. [Dept. of Radiology, Sahlgrenska Univ. Hospital, Goeteborg Univ. (Sweden); Jodal, U. [Dept. of Pediatrics, Sahlgrenska Univ. Hospital, Goeteborg Univ. (Sweden); Sixt, R. [Dept. of Pediatric Clinical Physiology, Sahlgrenska Univ. Hospital, Goeteborg Univ. (Sweden)

1998-07-01

Purpose: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. Material and Methods: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. Results: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. Conclusion: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known. (orig.)

Evaluation of DMSA scintigraphy and urography in assessing both acute and permanent renal damage in children

International Nuclear Information System (INIS)

Stokland, E.; Jacobsson, B.; Jodal, U.; Sixt, R.

1998-01-01

Purpose: To evaluate dimercaptosuccinic acid (DMSA) scintigraphy and urography in the detection of renal involvement in children with urinary tract infection (UTI) in order to identify patients with a high risk of developing renal damage. Material and Methods: A total of 157 children (median age 0.4 years, range 5 days to 5.8 years) with first-time symptomatic UTI were examined scintigraphy (with an assessment of renal area involvement) and urography at the time of UTI and 1 year later. All evaluations were made blindly. Results: Of the total 314 kidneys, 80 (25%) were abnormal at initial scintigraphy. Of these 80 kidneys, 44 (55%) had normalized at follow-up. Of the 234 initially normal kidneys, 29 (12%) were abnormal at follow-up. One year after UTI, abnormalities were seen in 59 children at scintigraphy and in 18 children at urography. Renal area involvement was larger and split function abnormalities more common in kidneys that were abnormal at both scintigraphy and urography than in kidneys with only scintigraphic abnormalities. Conclusion: Quantitation of renal area involvement and split renal function at early scintigraphy would seem to be useful in identifying patients at risk of developing renal damage. Urography at 1 year after infection identified mainly those with the most severe scintigraphic abnormalities. The clinical importance of scintigraphic abnormalities that are not confirmed by urography is not known. (orig.)

Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

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Carlos Wong-Baeza

2015-01-01

Full Text Available Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus

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Ünlü, Ozan; Zuily, Stephane; Erkan, Doruk

2016-01-01

Antiphospholipid syndrome (APS) is the association of thrombosis and/or pregnancy morbidity with antiphospholipid antibodies (aPL). Thirty to forty percent of systemic lupus erythematosus (SLE) patients are tested positive for aPL, which may have an impact on the SLE presentation, management, and prognosis. Compared with SLE patients without aPL, those with aPL have a higher prevalence of thrombosis, pregnancy morbidity, valve disease, pulmonary hypertension, livedo reticularis, thrombocytopenia, hemolytic anemia, acute/chronic renal vascular lesions, and moderate/severe cognitive impairment; worse quality of life; and higher risk of organ damage. The use of low-dose aspirin (LDA) is controversial for primary thrombosis and pregnancy morbidity prevention because of the lack of strong prospective controlled data. Similarly, the use of anticoagulation is controversial for patients with an aPL-related nephropathy. Until further studies are available, physicians should discuss the risk/benefits of LDA or anticoagulation as well as the available literature with patients. PMID:27708976

Qualitative and quantitative evaluation of renal parenchymal damage by 99mTc-DMSA planar and SPECT scintigraphy

International Nuclear Information System (INIS)

Itoh, Kazuo; Yamashita, Tetsufumi; Tsukamoto, Eriko; Nonomura, Katsuya; Furudate, Masayori; Koyanagi, Tomohiko

1995-01-01

The initial 99m Tc-DMSA studies carried out over a four year period in 229 patients with various heterogenic causes of lower urinary tract abnormalities were reviewed. Anatomical damage to the renal parenchyma was graded by means of planar and SPECT studies into a six group classification proposed by Monsour et al.: grade 0 (normal), I (equivocal), II (single defect), III (more than 2 defects), IV (contracted or small) and V (no visualization). Parenchymal uptake of 99m Tc-DMSA was quantitated from planar images at 2 hours postinjection by a computer assisted gamma camera method. SPECT studies could enhance the pick-up rate for parenchymal uptake defects by a factor of 1.5 in comparison with planar imaging. The incidence of anatomical damage to the renal parenchyma increased with a high radiological grade for VUR, and renal uptake per injection dose of 99m Tc-DMSA by the individual kidney significantly decreased in grades III and IV of the anatomical classification. These data revealed that 99m Tc-DMSA planar is still useful for evaluating gross structural damage and for quantitative evaluation of the kidney with computer assistance. SPECT scintigraphy is more effective in disclosing anatomical damage to the renal parenchyma than planar, although it needs further discussion as to whether SPECT may increase sensitivity with minimal or no adverse affect on specificity. (author)

Astragalus Injection for Hypertensive Renal Damage: A Systematic Review

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Tian Sun

2012-01-01

Full Text Available Objective. To evaluate the effectiveness of astragalus injection (a traditional Chinese patent medicine for patients with renal damage induced by hypertension according to the available evidence. Methods. We searched MEDLINE, China National Knowledge Infrastructure (CNKI, Chinese VIP Information, China Biology Medicine (CBM, and Chinese Medical Citation Index (CMCI, and the date of search starts from the first of database to August 2011. No language restriction was applied. We included randomized controlled trials testing astragalus injection against placebo or astragalus injection plus antihypertensive drugs against antihypertensive drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane review standards. Results. 5 randomized trials (involving 429 patients were included and the methodological quality was evaluated as generally low. The pooled results showed that astragalus injection was more effective in lowering β2-microglobulin (β2-MG, microalbuminuria (mAlb compared with placebo, and it was also superior to prostaglandin in lowering blood urea nitrogen (BUN, creatinine clearance rate (Ccr. There were no adverse effects reported in the trials from astragalus injection. Conclusions. Astragalus injection showed protective effects in hypertensive renal damage patients, although available studies are not adequate to draw a definite conclusion due to low quality of included trials. More rigorous clinical trials with high quality are warranted to give high level of evidence.

Dietary restriction delays the secretion of senescence associated secretory phenotype by reducing DNA damage response in the process of renal aging.

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Wang, Wenjuan; Cai, Guangyan; Chen, Xiangmei

2017-09-13

Dietary restriction (DR) has multiple and essential effects in protecting against DNA damage in model organisms. Persistent DNA damage plays a central role in the process of aging. Senescence-associated secretory phenotype (SASP), as a product of cellular aging, can accelerate the process of cellular senescence as a feedback. In this study, we directly observed whether a DR of 30% for 6months in aged rats could retard SASP by delaying the progression of DNA damage and also found the specific mechanism. The results revealed that a 30% DR could significantly improve renal pathology and some metabolic characteristics. The biomarkers and products of DNA damage were decreased in the process of renal aging on a 30% DR. A series of SASP, notably cytokine, chemokine, and growth factor, were obviously reduced by DR during renal aging. The phosphorylation levels of NF-κB and IκBα in aged kidneys of DR group were markedly reduced. These findings suggest that a 30% DR for 6months can delay renal aging and reduce the accumulation of SASP by retarding the progression of DNA damage and decreasing the transcription activity of NF-κB, thus providing a target to delay renal aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Reno-Cerebral Reflex Activates the Renin-Angiotensin System, Promoting Oxidative Stress and Renal Damage After Ischemia-Reperfusion Injury.

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Cao, Wei; Li, Aiqing; Li, Jiawen; Wu, Chunyi; Cui, Shuang; Zhou, Zhanmei; Liu, Youhua; Wilcox, Christopher S; Hou, Fan Fan

2017-09-01

A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury. Selective renal afferent denervation with capsaicin or renal denervation significantly attenuated IRI-induced activation of central RAS and brain inflammation. Central blockade of RAS or oxidative stress by intracerebroventricular (ICV) losartan or tempol reduced the renal ischemic injury score by 65% or 58%, respectively, and selective renal afferent denervation or reduction of sympathetic tone by ICV clonidine decreased the score by 42% or 52%, respectively (all p renal damage and dysfunction persisted after controlling blood pressure with hydralazine. This study uncovered a novel reflex pathway between ischemic kidney and the brain that sustains renal oxidative stress and local RAS activation to promote ongoing renal damage. These data suggest that the renal and cerebral renin-angiotensin axes are interlinked by a reno-cerebral sympathetic reflex that is activated by ischemia-reperfusion, which contributes to ischemia-reperfusion-induced brain inflammation and worsening of the acute renal injury. Antioxid. Redox Signal. 27, 415-432.

SLE disease patterns in a Danish population-based lupus cohort: an 8-year prospective study

DEFF Research Database (Denmark)

Laustrup, H; Voss, A; Green, A

2009-01-01

In 1995 all systemic lupus erythematosus (SLE) patients in the county of Funen were retrieved from four separate and independent sources as part of an 8-year prospective study to determine the pattern of disease activity and damage accumulation in a community based lupus cohort of predominantly...... Scandinavian ancestry. Incident cases were subsequently identified by surveillance of these sources. Established and new cases underwent annual, structured interviews, clinical examination and blood sampling. The Systemic Lupus Erythematosus Diseases Activity Index SLEDAI and Systemic Lupus International...

Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the Cardiovascular System. Focus on Microalbuminuria.

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Mulè, Giuseppe; Castiglia, Antonella; Cusumano, Claudia; Scaduto, Emilia; Geraci, Giulio; Altieri, Dario; Di Natale, Epifanio; Cacciatore, Onofrio; Cerasola, Giovanni; Cottone, Santina

2017-01-01

The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage. Data was supported by the very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis Consortium, which provided undisputable evidence that there is an inverse association between eGFR and CV risk. It is important to remember that in evaluating CV disease using renal parameters, GFR should be assessed simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate that also increased urinary albumin levels or proteinuria carry an increased risk of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values are not only predictors of progressive kidney failure, but also of all-cause and CV mortality, independent of each other and of traditional CV risk factors.Although subjects with ESRD are at the highest risk of CV diseases, there will likely be more events in subjects with mil-to-moderate renal dysfunction, because of its much higher prevalence.These findings are even more noteworthy when one considers that a mild reduction in renal function is very common in hypertensive patients.The current European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension recommend to sought in every patient signs of subclinical (or asymptomatic) renal damage. This was defined by the detection of eGFR between 30 mL/min/1.73 m 2 and 60 mL/min/1.73 m 2 or the

Pigmented villonodular synovitis of the hip in systemic lupus erythematosus: a case report

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Anders Hans-Joachim

2011-09-01

Full Text Available Abstract Introduction Pigmented villonodular synovitis is a rare disease of unknown etiology mostly affecting the knee and foot. Until now an association with autoimmune diseases has not been reported. Case presentation The diagnosis of systemic lupus erythematosus was made in a 15-year-old Caucasian girl based on otherwise unexplained fatigue, arthralgia, tenosynovitis, leukopenia, low platelets and the presence of antinuclear and deoxyribonucleic antibodies. At the age of 20 a renal biopsy revealed lupus nephritis class IV and she went into complete remission with mycophenolate mofetil and steroids. She was kept on mycophenolate mofetil for maintenance therapy. At the age of 24 she experienced a flare-up of lupus nephritis with nephrotic syndrome and new onset of pain in her right hip. Magnetic resonance imaging, arthroscopy and subtotal synovectomy identified pigmented villonodular synovitis as the underlying diagnosis. Although her systemic lupus erythematosus went into remission with another course of steroids and higher doses of mycophenolate mofetil, the pigmented villonodular synovitis persisted and she had to undergo open synovectomy to control her symptoms. Conclusion Systemic lupus erythematosus is associated with many different musculoskeletal manifestations including synovitis and arthritis. Pigmented villonodular synovitis has not previously been reported in association with systemic lupus erythematosus, but as its etiology is still unknown, the present case raises the question about a causal relationship between systemic lupus erythematosus and pigmented villonodular synovitis.

Effective Self-Management Interventions for Patients With Lupus: Potential Impact of Peer Mentoring.

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Williams, Edith M; Egede, Leonard; Faith, Trevor; Oates, James

2017-06-01

Systemic lupus erythematosus (SLE) is associated with significant mortality, morbidity and cost for the individual patient and society. In the United States, African Americans (AAs) have 3-4 times greater prevalence of lupus, risk of developing lupus at an earlier age and lupus-related disease activity, organ damage and mortality compared with whites. Evidence-based self-management interventions that incorporate both social support and health education have reduced pain, improved function and delayed disability among patients with lupus. However, AAs and women are still disproportionately affected by lupus. This article presents the argument that peer mentoring may be an especially effective intervention approach for AA women with SLE. SLE peers with a track record of success in lupus management and have a personal perspective that clinicians often lack. This commonality and credibility can establish trust, increase communication and, in turn, decrease disparities in healthcare outcomes. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

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Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

Cardiac and renal damage in the elderly hypertensive

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Jean Ribstein

2002-03-01

Full Text Available In the elderly patient with essential hypertension of long duration or de novo systolic hypertension, the prevalence of co-morbid conditions, be they apparent or not, the burden of associated diseases and the alteration in nutritional status and lifestyle, result in specific problems with regards to hypertension-related target organ damage. Accumulating data suggest that left ventricular (LV remodelling is a common finding in the nor-motensive elderly, and that LV hypertrophy (LVH will herald the development of heart failure in a fraction of patients with either systolic/diastolic or isolated systolic hypertension. Increased arterial stiffness, as well as impaired myocardial relaxation, reduced early diastolic filling and decreased ?-adrenergic responsiveness, contribute to the large prevalence of abnormalities in LV function in the elderly hypertensive. The response to exercise is clearly attenuated, and coronary heart disease, although highly prevalent, may be misdiagnosed because symptoms are altered. The elderly hypertensive is exquisitely sensitive to both volume depletion and excessive sodium intake, due to a marked sodium sensitivity of blood pressure (BP. A decline in renal blood flow and glomerular filtration rate (GFR is a common finding in the elderly. Although structural alterations attributed to age and hypertension may differ, hypertension is often looked upon as an accelerated form of ageing with regards to the heart and the kidney. Lifestyle modifications and initial monotherapy with a low-dose diuretic are warranted in the elderly hypertensive with no co-morbidity; a variety of specific approaches are considered when associated clinical conditions are present. Blockers of the renin-angiotensin system (RAS may be the preferred first-line agents in many patients with cardiac or renal damage.

Prevalence, incidence, and demographics of systemic lupus erythematosus and lupus nephritis from 2000 to 2004 among children in the US Medicaid beneficiary population.

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Hiraki, Linda T; Feldman, Candace H; Liu, Jun; Alarcón, Graciela S; Fischer, Michael A; Winkelmayer, Wolfgang C; Costenbader, Karen H

2012-08-01

To investigate the nationwide prevalence, incidence, and sociodemographics of systemic lupus erythematosus (SLE) and lupus nephritis among children in the US Medicaid beneficiary population. Children ages 3 years to Classification of Diseases, Ninth Revision [ICD-9] code of 710.0 for SLE, each >30 days apart) were identified from the US Medicaid Analytic eXtract database from 2000 to 2004. This database contains all inpatient and outpatient Medicaid claims for 47 US states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes for glomerulonephritis, proteinuria, or renal failure, each recorded >30 days apart. The prevalence and incidence of SLE and lupus nephritis were calculated among Medicaid-enrolled children overall and within sociodemographic groups. Of the 30,420,597 Medicaid-enrolled children during these years, 2,959 were identified as having SLE. The prevalence of SLE was 9.73 (95% confidence interval [95% CI] 9.38-10.08) per 100,000 Medicaid-enrolled children. Among the children with SLE, 84% were female, 40% were African American, 25% were Hispanic, 21% were White, and 42% resided in the South region of the US. Moreover, of the children with SLE, 1,106 (37%) had lupus nephritis, representing a prevalence of 3.64 (95% CI 3.43-3.86) per 100,000 children. The average annual incidence of SLE was 2.22 cases (95% CI 2.05-2.40) and that of lupus nephritis was 0.72 cases (95% CI 0.63-0.83) per 100,000 Medicaid enrollees per year. The prevalence and incidence rates of SLE and lupus nephritis increased with age, were higher in girls than in boys, and were higher in all non-White racial/ethnic groups. In the current study, the prevalence and incidence rates of SLE among Medicaid-enrolled children in the US are high compared to studies in other populations. In addition, these data represent the first population-based estimates of the prevalence and incidence of lupus nephritis in the US to date. Copyright © 2012 by the American

Historical development of the renal histopathology services in Malaysia.

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Looi, Lai-Meng; Cheah, Phaik-Leng

2009-06-01

Western-style medicine was introduced to Malaya by the Portuguese, Dutch and British between the 1500s and 1800s. Although the earliest pathology laboratories were developed within hospitals towards the end of the 19th Century, histopathology emerged much later than the biochemistry and bacteriology services. The University Departments of Pathology were the pioneers of the renal histopathology diagnostic services. The Department of Pathology, University of Malaya (UM) received its first renal biopsy on 19 May 1968. Hospital Universiti Kebangsaan Malaysia (HUKM) and Hospital Universiti Sains Malaysia (HUSM) started their services in 1979 and 1987 respectively. It is notable that the early services in these University centres caterred for both the university hospitals and the Ministry of Health (MOH) until the mid-1990s when MOH began to develop its own services, pivoted on renal pathologists trained through Fellowship programmes. Currently, key centres in the MOH are Kuala Lumpur Hospital, Sultanah Aminah Hospital Johor Bahru and Malacca Hospital. With the inclusion of renal biopsy interpretation in the Master of Pathology programmes, basic renal histopathology services became widely available throughout the country from 2000. This subsequently filtered out to the private sector as more histopathologists embraced private practice. There is now active continuing professional development in renal histopathology through clinicopathological dicussions, seminars and workshops. Renal research on amyloid nephropathy, minimal change disease, IgA nephropathy, fibrillary glomerulonephritis, lupus nephritis and microwave technology have provided an insight into the patterns of renal pathology and changing criteria for biopsy. More recently, there has been increasing involvement of renal teams in clinical trials, particularly for lupus nephritis and renal transplant modulation.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

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Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

2017-06-01

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( Plupus erythematosus patients in comparison to controls ( P lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Blood oxygen level dependent magnetic resonance imaging for detecting pathological patterns in lupus nephritis patients: a preliminary study using a decision tree model.

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Shi, Huilan; Jia, Junya; Li, Dong; Wei, Li; Shang, Wenya; Zheng, Zhenfeng

2018-02-09

Precise renal histopathological diagnosis will guide therapy strategy in patients with lupus nephritis. Blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) has been applicable noninvasive technique in renal disease. This current study was performed to explore whether BOLD MRI could contribute to diagnose renal pathological pattern. Adult patients with lupus nephritis renal pathological diagnosis were recruited for this study. Renal biopsy tissues were assessed based on the lupus nephritis ISN/RPS 2003 classification. The Blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) was used to obtain functional magnetic resonance parameter, R2* values. Several functions of R2* values were calculated and used to construct algorithmic models for renal pathological patterns. In addition, the algorithmic models were compared as to their diagnostic capability. Both Histopathology and BOLD MRI were used to examine a total of twelve patients. Renal pathological patterns included five classes III (including 3 as class III + V) and seven classes IV (including 4 as class IV + V). Three algorithmic models, including decision tree, line discriminant, and logistic regression, were constructed to distinguish the renal pathological pattern of class III and class IV. The sensitivity of the decision tree model was better than that of the line discriminant model (71.87% vs 59.48%, P decision tree model was equivalent to that of the line discriminant model (63.87% vs 63.73%, P = 0.939) and higher than that of the logistic regression model (63.87% vs 38.0%, P decision tree model was greater than that of the line discriminant model (0.765 vs 0.629, P Decision tree models constructed using functions of R2* values may facilitate the prediction of renal pathological patterns.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension

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Patricia Fernández-Llama

2017-12-01

Full Text Available Background/Aims: Central blood pressure (BP has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. Methods: Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis office BP and ambulatory BP monitoring (ABPM data and aortic pulse wave velocity (PWV were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. Results: Fifty-four patients (25.9% were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine or an estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP and pulse pressure (PP, and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. Conclusion: Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice.

Cuff-Based Oscillometric Central and Brachial Blood Pressures Obtained Through ABPM are Similarly Associated with Renal Organ Damage in Arterial Hypertension.

Science.gov (United States)

Fernández-Llama, Patricia; Pareja, Júlia; Yun, Sergi; Vázquez, Susana; Oliveras, Anna; Armario, Pedro; Blanch, Pedro; Calero, Francesca; Sierra, Cristina; de la Sierra, Alejandro

2017-01-01

Central blood pressure (BP) has been suggested to be a better estimator of hypertension-associated risks. We aimed to evaluate the association of 24-hour central BP, in comparison with 24-hour peripheral BP, with the presence of renal organ damage in hypertensive patients. Brachial and central (calculated by an oscillometric system through brachial pulse wave analysis) office BP and ambulatory BP monitoring (ABPM) data and aortic pulse wave velocity (PWV) were measured in 208 hypertensive patients. Renal organ damage was evaluated by means of the albumin to creatinine ratio and the estimated glomerular filtration rate. Fifty-four patients (25.9%) were affected by renal organ damage, displaying either microalbuminuria (urinary albumin excretion ≥30 mg/g creatinine) or an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Compared to those without renal abnormalities, hypertensive patients with kidney damage had higher values of office brachial systolic BP (SBP) and pulse pressure (PP), and 24-h, daytime, and nighttime central and brachial SBP and PP. They also had a blunted nocturnal decrease in both central and brachial BP, and higher values of aortic PWV. After adjustment for age, gender, and antihypertensive treatment, only ABPM-derived BP estimates (both central and brachial) showed significant associations with the presence of renal damage. Odds ratios for central BP estimates were not significantly higher than those obtained for brachial BP. Compared with peripheral ABPM, cuff-based oscillometric central ABPM does not show a closer association with presence of renal organ damage in hypertensive patients. More studies, however, need to be done to better identify the role of central BP in clinical practice. © 2017 The Author(s). Published by S. Karger AG, Basel.

Pulmonary manifestations of systemic lupus erythematosus

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Yang, Kee Hyuk; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Joo, Kyung Bin; Hahm, Chang Kok; Lee, Seung Ro [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

2004-02-01

Pulmonary involvement is more common in systemic lupus erythematosus (SLE) than in any other connective tissue disease, and more than half of patients with SLE suffer from respiratory dysfunction during the course of their illness. Although sepsis and renal disease are the most common causes of death in SLE, lung disease is the predominant manifestation and is an indicator of overall prognosis. Respiratory disease may be due to direct involvement of the lung or as a secondary consequence of the effect of the disease on other organ systems.

Pulmonary manifestations of systemic lupus erythematosus

International Nuclear Information System (INIS)

Yang, Kee Hyuk; Choi, Yo Won; Jeon, Seok Chol; Park, Choong Ki; Joo, Kyung Bin; Hahm, Chang Kok; Lee, Seung Ro

2004-01-01

Pulmonary involvement is more common in systemic lupus erythematosus (SLE) than in any other connective tissue disease, and more than half of patients with SLE suffer from respiratory dysfunction during the course of their illness. Although sepsis and renal disease are the most common causes of death in SLE, lung disease is the predominant manifestation and is an indicator of overall prognosis. Respiratory disease may be due to direct involvement of the lung or as a secondary consequence of the effect of the disease on other organ systems

Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

Science.gov (United States)

Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

2017-01-01

Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane.

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Summers, S A; Odobasic, D; Khouri, M B; Steinmetz, O M; Yang, Y; Holdsworth, S R; Kitching, A R

2014-06-01

Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A(-/-) mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G(+)) and macrophages (F4/80(+)) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4(+) T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A(-/-) mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A. © 2014 British Society for Immunology.

The effect of zinc on healing of renal damage in rats.

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Salehipour, Mehdi; Monabbati, Ahmad; Ensafdaran, Mohammad Reza; Adib, Ali; Babaei, Amir Hossein

2017-07-01

Several studies have previously been performed to promote kidney healing after injuries. Objectives: The aim of this study was to investigate the effect of zinc on renal healing after traumatic injury in rats. Forty healthy female rats were selected and one of their kidneys was incised. Half of the incisions were limited only to the cortex (renal injury type I) and the other ones reached the pelvocalyceal system of the kidney (renal injury type II). All the rats in the zinc treated group (case group) received 36.3 mg zinc sulfate (contained 8.25 mg zinc) orally. After 28 days, the damaged kidneys were removed for histopathological studies. In the rats with type I injury, kidney inflammation of the case group was significantly lower than that of the control group. However, the result was not significant in rats with type II injury. Tissue loss and granulation tissue formation were significantly lower in the case group than the control group in both type I and II kidney injuries. Overall, Zinc can contribute to better healing of the rat's kidneys after a traumatic injury.

Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort.

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Riveros Frutos, A; Casas, I; Rúa-Figueroa, I; López-Longo, F J; Calvo-Alén, J; Galindo, M; Fernández-Nebro, A; Pego-Reigosa, J M; Olivé Marqués, A

2017-06-01

Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18-92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p lupus nephritis was more common in men, being present in 155 (44.8%) of males versus 933 (29%) of females ( p  50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50 years have an increased risk of mortality. In Caucasians, age at diagnosis and symptom onset is higher in men than in women. The diagnostic delay is shorter in men. Male SLE patients present more cardiovascular comorbidities, and also more serositis, adenopathies, splenomegaly, renal involvement, convulsion, thrombosis, and lupus anticoagulant positivity than women.

Hashimoto thyroiditis, anti-thyroid antibodies and systemic lupus erythematosus.

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Posselt, Rayana T; Coelho, Vinícius N; Skare, Thelma L

2018-01-01

To study the prevalence of Hashimoto thyroiditis (HT), anti-thyroid autoantibodies (anti-thyroglobulin or TgAb and thyroperoxidase or TPOAb) in systemic lupus erythematosus (SLE) patients. To analyze if associated HT, TgAb and/or TPOAb influence clinical or serological profiles, disease activity and/or its cumulative damage. Three hundred and one SLE patients and 141 controls were studied for thyroid stimulating hormone, thyroxin, TgAb and TPOAb by chemiluminescence and immunometric assays. Patients' charts were reviewed for serological and clinical profiles. Activity was measured by SLE Disease Activity Index and cumulative damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. SLE patients were divided into: (i) with HT; (ii) with anti-thyroid antibodies but without HT; and (iii) without HT and without anti-thyroid antibodies, and were then compared. Furthermore, SLE patients were compared according to the number of positive anti-thyroid antibodies. Hashimoto thyroiditis prevalence in SLE was 12.6% and 5.6% in controls (P = 0.02; odds ratio = 2.4; 95% CI = 1.09-5.2). Lupus patients with HT had less malar rash (P = 0.02) and more anti-Sm (P = 0.04). Anti-Sm was more common in those with two anti-thyroid antibodies than in those with one or negative. The presence of HT or the number of positive autoantibodies did not associate either with disease activity (P = 0.95) or with cumulative damage (P = 0.98). There is a two-fold increased risk of HT in SLE patients. Anti-Sm antibodies favor this association and also double antibody positivity. Disease activity and cumulative damage are not related to HT or with autoantibodies. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus

DEFF Research Database (Denmark)

Fenton, Kristin Andreassen; Mjelle, Janne Erikke; Jacobsen, Søren

2008-01-01

) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis...... to the evolution of lupus nephritis in human SLE....

Hydroxychloroquine in systemic lupus erythematosus (SLE).

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Ponticelli, C; Moroni, G

2017-03-01

Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE). Areas covered: In this review the mechanisms of action, the efficacy, and the safety of HCQ in the management of patients with SLE have been reviewed. HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ. Expert opinion: HCQ may offer several advantages not only in patients with mild SLE but can also exert important beneficial effects in lupus patients with organ involvement and in pregnant women. The drug has a low cost and few side effects. These characteristics should encourage a larger use of HCQ, also in lupus patients with organ involvement.

Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L).

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Alarcón, Graciela S; McGwin, Gerald; Bertoli, Ana M; Fessler, Barri J; Calvo-Alén, Jaime; Bastian, Holly M; Vilá, Luis M; Reveille, John D

2007-09-01

In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival. Patients with SLE from the multiethnic LUMINA (LUpus in MInorities: NAture vs nurture) cohort were studied. A case-control study was performed within the context of this cohort in which deceased patients (cases) were matched for disease duration (within 6 months) with alive patients (controls) in a proportion of 3:1. Survival was the outcome of interest. Propensity scores were derived by logistic regression to adjust for confounding by indication as patients with SLE with milder disease manifestations are more likely to be prescribed hydroxychloroquine. A conditional logistic regression model was used to estimate the risk of death and hydroxychloroquine use with and without the propensity score as the adjustment variable. There were 608 patients, of whom 61 had died (cases). Hydroxychloroquine had a protective effect on survival (OR 0.128 (95% CI 0.054 to 0.301 for hydroxychloroquine alone and OR 0.319 (95% CI 0.118 to 0.864) after adding the propensity score). As expected, the propensity score itself was also protective. Hydroxychloroquine, which overall is well tolerated by patients with SLE, has a protective effect on survival which is evident even after taking into consideration the factors associated with treatment decisions. This information is of importance to all clinicians involved in the care of patients with SLE.

A liposomal steroid nano-drug for treating systemic lupus erythematosus.

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Moallem, E; Koren, E; Ulmansky, R; Pizov, G; Barlev, M; Barenholz, Y; Naparstek, Y

2016-10-01

Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model. In the present work we have evaluated the therapeutic effect of the above liposome-based steroidal (MPS) nano-drug in the MRL-lpr/lpr murine model of SLE and compared it with similar doses of the free MPS. MRL-lpr/lpr mice were treated with daily injections of free MPS or weekly injections of 10% dextrose, empty nano-liposomes or the steroidal nano-drug and the course of their disease was followed up to the age of 24 weeks. Treatment with the steroidal nano-drug was found to be significantly superior to the free MPS in suppressing anti-dsDNA antibody levels, proliferation of lymphoid tissue and renal damage, and in prolonging survival of animals. This significant superiority of our liposome based steroidal nano-drug administered weekly compared with daily injections of free methylprednisolone hemisuccinate in suppressing murine lupus indicates this glucocorticoid nano-drug formulation may be a good candidate for the treatment of human SLE. © The Author(s) 2016.

Impact of Hot Environment on Fluid and Electrolyte Imbalance, Renal Damage, Hemolysis, and Immune Activation Postmarathon

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Rodrigo Assunção Oliveira

2017-01-01

Full Text Available Previous studies have demonstrated the physiological changes induced by exercise exposure in hot environments. We investigated the hematological and oxidative changes and tissue damage induced by marathon race in different thermal conditions. Twenty-six male runners completed the São Paulo International Marathon both in hot environment (HE and in temperate environment (TE. Blood and urine samples were collected 1 day before, immediately after, 1 day after, and 3 days after the marathon to analyze the hematological parameters, electrolytes, markers of tissue damage, and oxidative status. In both environments, the marathon race promotes fluid and electrolyte imbalance, hemolysis, oxidative stress, immune activation, and tissue damage. The marathon runner’s performance was approximately 13.5% lower in HE compared to TE; however, in HE, our results demonstrated more pronounced fluid and electrolyte imbalance, renal damage, hemolysis, and immune activation. Moreover, oxidative stress induced by marathon in HE is presumed to be related to protein/purine oxidation instead of other oxidative sources. Fluid and electrolyte imbalance and protein/purine oxidation may be important factors responsible for hemolysis, renal damage, immune activation, and impaired performance after long-term exercise in HE. Nonetheless, we suggested that the impairment on performance in HE was not associated to the muscle damage and lipoperoxidation.

Renal parenchymal damage on DMSA-scintigraphy in pelviureteric obstruction

International Nuclear Information System (INIS)

Kullendorff, C.M.; Evander, E.

1989-01-01

During a 1.5 year period 21 children were investigated with 99-m-technetium dimercaptosuccini acid (DMSA) before operation for hydronephrosis due to pelviureteric obstruction. The age at investigation was 0.2-11.5 years. Fourty-two kidneys were examined. Hydronephrosis existed on the right side in 8 cases, left side in 9 and bilateral in 4 cases. Seventeen kidneys had no obstruction. The scintigraphy was interpreted as normal in 19 kidneys. Decreased isotope uptake was found in 23 kidneys and localized to the upper pole area in 19 kidneys. middle-lateral part in 7, lower pole area in 15 and the middle-medial part in 12 kidneys. There were no predominance for any part of the kidney to be affected by parenchymal damage. In 8 children investigated before the age of 1 year, 4 of 10 hydronephrotic kidneys revealed normal DMSA scintigram. DMSA scintigraphy delineates functioning renal parenchyma. It can be recommended as a routine method for evaluation of the renal parenchyma before surgery and for follow up studies in all ages of childhood

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure

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Abderrahim Nemmar

2016-05-01

Full Text Available Background/Aims: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Methods: Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks, which is known to involve inflammation and oxidative stress. DEP (0.5m/kg was intratracheally (i.t. instilled every 4th day for 4 weeks (7 i.t. instillation. Four days following the last exposure to either DEP or saline (control, various renal endpoints were measured. Results: While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Conclusion: Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic

A Prospective Study of the Impact of Current Poverty, History of Poverty, and Exiting Poverty on Accumulation of Disease Damage in Systemic Lupus Erythematosus.

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Yelin, Edward; Trupin, Laura; Yazdany, Jinoos

2017-08-01

To estimate the effect of current poverty, number of years in poverty, and exiting poverty on disease damage accumulation in systemic lupus erythematosus (SLE). For this study, 783 patients with SLE were followed up from 2003 to 2015 through annual structured interviews. Respondents were categorized in each year by whether they had a household income of ≤125% of the US federal poverty level. Linear and logistic regression analyses were used to assess the impact of poverty in 2009, number of years in poverty between 2003 and 2009, and permanent exits from poverty as of 2009 on the extent of disease damage (according to the Brief Index of Lupus Damage [BILD] score) or accumulation of a clinically meaningful increase in disease damage (defined as a minimum 2-point increase in the BILD damage score) by 2015. After adjustment for sociodemographic features, health care characteristics, and health behaviors, poverty in 2009 was associated with an increased level of accumulated disease damage in 2015 (mean difference in BILD damage score between poor and non-poor 0.62 points, 95% confidence interval [95% CI] 0.25-0.98) and increased odds of a clinically important increase in damage (odds ratio [OR] 1.67, 95% CI 0.98-2.85). Being poor in every year between 2003 and 2009 was associated with greater damage (mean change in BILD score 2.45, 95% CI 1.88-3.01) than being poor for one-half or more of those years (mean change in BILD score 1.45, 95% CI 0.97-1.93), for fewer than one-half of those years (mean change in BILD score 1.49, 95% CI 1.10-1.88), or for none of those years (mean change in BILD score 1.34, 95% CI 1.20-1.49). Those exiting poverty permanently had similar increases in disease damage (mean change in BILD score 1.30, 95% CI 0.90-1.69) as those who were never in poverty (mean change in BILD score 1.36, 95% CI 1.23-1.50) but much less damage than those who remained in poverty (mean change in BILD score 1.98, 95% CI 1.59-2.38). The effects of current poverty

The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model.

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Willemien L Verloop

Full Text Available Recently, the efficacy of renal denervation (RDN has been debated. It is discussed whether RDN is able to adequately target the renal nerves.We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology.We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01. In contrast, renal resistance reserve increased from 1.74 (1.28 to 1.88 (1.17 (P = 0.02 during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14% nerves per pig were observed within a lesion area. Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05 at three weeks of follow-up.Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN.

The Effects of Renal Denervation on Renal Hemodynamics and Renal Vasculature in a Porcine Model

Science.gov (United States)

Verloop, Willemien L.; Hubens, Lisette E. G.; Spiering, Wilko; Doevendans, Pieter A.; Goldschmeding, Roel; Bleys, Ronald L. A. W.; Voskuil, Michiel

2015-01-01

Rationale Recently, the efficacy of renal denervation (RDN) has been debated. It is discussed whether RDN is able to adequately target the renal nerves. Objective We aimed to investigate how effective RDN was by means of functional hemodynamic measurements and nerve damage on histology. Methods and Results We performed hemodynamic measurements in both renal arteries of healthy pigs using a Doppler flow and pressure wire. Subsequently unilateral denervation was performed, followed by repeated bilateral hemodynamic measurements. Pigs were terminated directly after RDN or were followed for 3 weeks or 3 months after the procedure. After termination, both treated and control arteries were prepared for histology to evaluate vascular damage and nerve damage. Directly after RDN, resting renal blood flow tended to increase by 29±67% (P = 0.01). In contrast, renal resistance reserve increased from 1.74 (1.28) to 1.88 (1.17) (P = 0.02) during follow-up. Vascular histopathology showed that most nerves around the treated arteries were located outside the lesion areas (8±7 out of 55±25 (14%) nerves per pig were observed within a lesion area). Subsequently, a correlation was noted between a more impaired adventitia and a reduction in renal resistance reserve (β: -0.33; P = 0.05) at three weeks of follow-up. Conclusion Only a small minority of renal nerves was targeted after RDN. Furthermore, more severe adventitial damage was related to a reduction in renal resistance in the treated arteries at follow-up. These hemodynamic and histological observations may indicate that RDN did not sufficiently target the renal nerves. Potentially, this may explain the significant spread in the response after RDN. PMID:26587981

Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy.

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Jinfeng Yang

Full Text Available To characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE and its complication lupus nephritis (LN in a large cohort of patients.Clinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002-2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG. Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain.Simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001. Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery.Simultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG may indicate severe nephropathy in patients with SLE.

IgA nephropathy in systemic lupus erythematosus patients: case report and literature review

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Leonardo Sales da Silva

2016-06-01

Full Text Available Abstract Systemic erythematosus lupus (SLE is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non‐lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN, the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1,280, nuclear fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non‐SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in the short and long term.

Independent association of glucocorticoids with damage accrual in SLE.

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Apostolopoulos, Diane; Kandane-Rathnayake, Rangi; Raghunath, Sudha; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F

2016-01-01

To determine factors associated with damage accrual in a prospective cohort of patients with SLE. Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI. Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.

Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

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Lech, Maciej; Kulkarni, Onkar P.; Pfeiffer, Stephanie; Savarese, Emina; Krug, Anne; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2008-01-01

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. PMID:18644972

Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines.

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Navarra, S V; Tanangunan, R M D V; Mikolaitis-Preuss, R A; Kosinski, M; Block, J A; Jolly, M

2013-03-01

LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural validation results of the LupusPRO English-language version among Filipino SLE patients. The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed. A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit. English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

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Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a

Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease

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Mohammad S Alzahri

2015-01-01

Full Text Available Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.

The Swedish infant high-grade reflux trial: UTI and renal damage.

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Nordenström, Josefin; Sjöström, Sofia; Sillén, Ulla; Sixt, Rune; Brandström, Per

2017-04-01

High-grade vesicoureteral reflux (VUR) in children is associated with recurrent urinary tract infection (UTI) and renal damage. Breakthrough UTI despite continuous antibiotic prophylaxis (CAP) during the first years of life is a matter of concern and evokes early intervention. We investigated whether early endoscopic treatment (ET) of VUR grade 4-5 can reduce the risk of UTI recurrence and renal scarring. This prospective, randomized, controlled, multicentre, 1-year follow-up trial comprised 77 infants, UTIs were reported. There were 27 recurrent febrile UTIs in 6 (16%) children in the ET group and in 10 (26%) in the CAP group (p = 0.43), in eight (36%) girls and eight (15%) boys (p = 0.039). Successful VUR outcome (VUR 0-2) was seen in 22 (59%) in the ET and eight (21%) in the CAP group (p = 0.0014). Multiple recurrences were only seen in patients with persistent dilating reflux at follow-up (p = 0.019). Deterioration on scintigraphy was seen in eight children (9 kidneys) with no difference between treatment groups (p = 0.48) or sex (p = 0.17). Renal deterioration was associated with high bladder capacity (BC) and large residual volume (PVR) at 1 year (p = 0.0092 and p = 0.041). Six of the eight children with renal deterioration had a recurrent UTI (p = 0.0032). Seven of nine renal units with deterioration were seen in children with persistent VUR 3-5 at follow-up. Univariable logistic regression identified female sex and high PVR as positive predictors for recurrent UTI (p = 0.039 and 0.034) and high PVR tended to predict renal deterioration (p = 0.053). No differences between the treatment groups regarding recurrent UTI and renal deterioration could be found. Increased PVR and female sex were positive predictors for UTI recurrences. VUR grade at follow-up was correlated to UTI recurrence and renal deterioration. This study did not show any difference between ET and CAP in reducing the risk of UTI recurrence or renal deterioration. The rate

Different Types of Lupus

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... Twitter Facebook Pinterest Email Print Different types of lupus Lupus Foundation of America September 18, 2017 Resource ... lupus. Learn more about each type below. Systemic lupus erythematosus Systemic lupus is the most common form ...

Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress.

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Minglong Shao

Full Text Available Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR plays a critical role in attenuating insulin resistance, inflammation and oxidative stress.The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms.Mice were fed with a high-fat diet (HFD, 40% of calories from fat for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured.HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2 expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks.These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress.

Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

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Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

2017-11-01

The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

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Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

2016-12-01

Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

Neuropsychiatric events attributed to systemic lupus erythematosus: a single center study form pakistan

International Nuclear Information System (INIS)

Mumtaz, S.; Rasheed, U.; Zammurrad, S.; Aziz, W.

2017-01-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a relatively common and potentially serious manifestation of SLE. This study was designed to collect evidence about clinical and demographic characteristics of patients with NPSLE in a Pakistani lupus cohort. ethodology: This cross-sectional study was conducted at Department of Rheumatology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan between July 2016 and December 2016. Patients fulfilling diagnostic criteria for SLE as defined by ACR were enrolled. For detection of neuropsychiatric involvement the One-Hour Neuropsychological Battery proposed by the ACR was performed. Neuropsychiatric manifestations were classified into major and minor. Relationship of presence and severity of individual neuropsychiatric manifestations to disease duration in years and organ damage using SLICC/ACR-DI was studied. esults: Out of 100 SLE patients, there were 96 females and 4 males (female to male ratio of 24:1). Mean age of all participants was 30.99 years (range 17-72 years) and average disease duration at the time of enrolment was 3.89 years. Neuropsychiatric manifestations were observed in 84 patients. 20 out of these 84 patients (23.8%) had major neurological manifestations including seizures (13 patients), altered consciousness (10 patients) and cerebro-vascular accident (5 patients). While 7 out of these 84 patients (8.3%) had major psychiatric manifestations including psychosis (5 patients) and depression with suicidal ideation (2 patients). All major neurological manifestations occurred beyond and major psychiatric manifestations occurred within 2 years of diagnosis of SLE. Minor psychiatric manifestations observed included severe anxiety (52 patients), cognitive impairment (43 patients) and mood disorder (25 patients). No statistically significant difference in mean SLICC/ACR-DI score was observed between NPSLE patients and non-NPSLE patients when points received for neurologically related damage were

Development of systemic lupus erythematosus in-patient with systemic sclerosis

International Nuclear Information System (INIS)

Martinez, Jose B; Medina, Yimmy F; Restrepo, Jose Felix; Rondon, Federico; Iglesias G, Antonio

2005-01-01

A 56 years old woman with systemic sclerosis consult by rapidly progressive deterioration of his pulmonary and renal function developing a superposition syndrome with systemic lupus erythematosus, unusual presentation that respond to high doses of corticosteroid and ciclophos- phamide. This is the first reported case in the literature of a superposition syndrome that begins with systemic sclerosis. The clinical finding, immunologic profile and its possible association are discussed

DNA repair and U.V.-light sensitivity of the lymphocytes in discoid lupus erythematosus

International Nuclear Information System (INIS)

Horkay, I.; Nagy, E.; Tamasi, P.; Szabo, M.; Csongor, J.

1975-01-01

Excision repair and cell damage induced by U.V.-light were studied in peripheral lymphocyte cultures derived from patients with discoid lupus erythematosus. Radioactivity was measured by means of a Packard liquid-scintillation counter, cell damage after U.V.-irradiation was estimated by vital staining with trypan-blue and by decrease of the cell-count. Repair incorporation of mostly normal rate could be demonstrated in the lymphocyte cultures of all the 22 patients with discoid lupus erythematosus. The cell damaging effect of U.V.-light was more increased in these cultures than in those of the normal controls. The repair inhibiting effect of chloroquine administered orally in therapeutic doses to the patients was generally slight and incidental. The possible correlation of the findings is discussed

Evaluating fatigue in lupus-prone mice: preliminary assessments.

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Meeks, Allison; Larson, Susan J

2012-01-01

Fatigue is a debilitating condition suffered by many as the result of chronic disease, yet relatively little is known about its biological basis or how to effectively manage its effects. This study sought to evaluate chronic fatigue by using lupus-prone mice and testing them at three different time periods. Lupus-prone mice were chosen because fatigue affects over half of patients with Systemic Lupus Erythematosus. Eleven MLR⁺/(+) (genetic controls) and twelve MLR/MpJ-Fas/J (MRL/lpr; lupus-prone) mice were tested three times: once at 12, 16 and 20 weeks of age. All mice were subjected to a variety of behavioral tests including: forced swim, post-swim grooming, running wheel, and sucrose consumption; five of the MLR⁺/(+) and five of the MLR/lpr mice were also tested on a fixed ratio-25 operant conditioning task. MRL/lpr mice showed more peripheral symptoms of lupus than controls, particularly lymphadenopathy and proteinuria. Lupus mice spent more time floating during the forced swim test and traveled less distance in the running wheel at each testing period. There were no differences between groups in post-swim grooming or in number of reinforcers earned in the operant conditioning task indicating the behavioral changes were not likely due simply to muscle weakness or motivation. Correlations between performance in the running wheel, forced swim test and sucrose consumption were conducted and distance traveled in the running wheel was consistently negatively correlated with time spent floating. Based on these data, we conclude that the lupus-prone mice were experiencing chronic fatigue and that running wheel activity and floating during a forced swim test can be used to evaluate fatigue, although these data cannot rule out the possibility that both fatigue and a depressive-like state were mediating these effects. Copyright © 2011 Elsevier Inc. All rights reserved.

Validity of LupusQoL-China for the assessment of health related quality of life in Chinese patients with systemic lupus erythematosus.

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Su-li Wang

Full Text Available OBJECTIVES: To adapt and assess the validity and reliability of LupusQoL for use in Chinese patients with systemic lupus erythematosus (SLE. METHODS: Debriefing interviews of subjects with SLE guided the language modifications of the tool. The process of adaptation proceeded according to the guideline and pre-testing results of LupusQoL-China. 220 SLE patients completed LupusQoL-China and a generic preference-based measurement of health EuroQoL scale (EQ-5D, and 20 patients repeated them after 2 weeks. Internal consistency (ICR and test-retest (TRT reliability, convergent and discriminant validity were examined. Factor analysis and Rasch analysis were performed. RESULTS: The mean (SD age of the 208 subjects with SLE was 33.93 (± 9.19 years. ICR and TRT of the eight domains ranged from 0.811 to 0.965 and 0.836 to 0.974, respectively. The LupusQoL-China domains demonstrated substantial evidence of construct validity when compared with equivalent domains on the EQ-5D (physical health and usual activities r = -0.63, pain and pain/discomfort r = -0.778, emotional health and anxiety/depression r = -0.761, planning and usual activities r = -0.560. Most LupusQoL-China domains could discriminate patients with varied disease activities and end-organ damage (according to SELENA-SLEDAI and SLICC-DI. The principal component analysis revealed six factors, and confirmatory factor analysis result of which is similar to eight factors model. CONCLUSIONS: These results provide evidence that the LupusQoL-China is valid as a disease-specific HRQoL assessment tool for Chinese patients with SLE.

Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney.

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Kelsen, Silvia; He, Xiaochen; Chade, Alejandro R

2012-08-15

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution

Regulatory Effect of Melatonin on Cytokine Disturbances in the Pristane-Induced Lupus Mice

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Ling-ling Zhou

2010-01-01

Full Text Available Systemic lupus erythematosus (SLE develops in relation to many environmental factors. In our opinion, it is more important to investigate the effect of melatonin on the environmental- related SLE. In the present study, 0.5 ml pristane were used to induce SLE in female BALB/c mice. Melatonin (0.01, 0.1, 1.0 mg/kg was orally administered immediately after pristane-injection for 24 weeks. IgM anti ssDNA and histone antibodies were detected after 0, 1, 2, 4, 8 weeks pristane injection. The levels of IL-2, IL-6 and IL-13 were detected after 24 weeks. Renal lesions were also observed. The results showed that melatonin antagonized the increasing levels of IgM anti ssDNA and histone autoantibodies. Melatonin could also decrease the IL-6 and IL-13 production and increase the IL-2 production. Besides, melatonin could lessen the renal lesions caused by pristane. These results suggested that melatonin has a beneficial effect on pristane-induced lupus through regulating the cytokines disturbances.

[Definition and biomarkers of acute renal damage: new perspectives].

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Seijas, M; Baccino, C; Nin, N; Lorente, J A

2014-01-01

The RIFLE and AKIN criteria have definitely help out to draw attention to the relationship between a deterioration of renal function that produces a small increase in serum creatinine and a worse outcome. However, the specific clinical utility of using these criteria remains to be well-defined. It is believed that the main use of these criteria is for the design of epidemiological studies and clinical trials to define inclusion criteria and objectives of an intervention. AKI adopting term, re-summoning former ARF terminology, it is appropriate to describe the clinical condition characterized by damage to kidney, in the same way as the term is used to describe acute lung damage where the lung injury situation still has not increased to a situation of organ failure (dysfunction). The serum and urine biomarkers (creatinine, urea, and diuresis) currently in use are not sensitive or specific for detecting kidney damage, limiting treatment options and potentially compromising the outcome. New biomarkers are being studied in order to diagnose an earlier and more specific AKI, with the potential to change the definition criteria of AKI with different stages, currently based in diuresis and serum creatinine. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?

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Catoggio, L J; Soriano, E R; Imamura, P M; Wojdyla, D; Jacobelli, S; Massardo, L; Chacón Díaz, R; Guibert-Toledano, M; Alvarellos, A; Saurit, V; Manni, J A; Pascual-Ramos, V; Silva de Sauza, A W; Bonfa, E; Tavares Brenol, J C; Ramirez, L A; Barile-Fabris, L A; De La Torre, I Garcia; Alarcón, G S; Pons-Estel, B A

2015-07-01

To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (lupus, adjusting for other variables. Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p  0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements. © The Author(s) 2014.

The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus.

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Lewis, Myles J; Jawad, Ali S

2017-04-01

In this in-depth review, we examine the worldwide epidemiology of SLE and summarize current knowledge on the influence of race/ethnicity on clinical manifestations, disease activity, damage accumulation and outcome in SLE. Susceptibility to SLE has a strong genetic component, and trans-ancestral genetic studies have revealed a substantial commonality of shared genetic risk variants across different genetic ancestries that predispose to the development of SLE. The highest increased risk of developing SLE is observed in black individuals (incidence 5- to 9-fold increased, prevalence 2- to 3-fold increased), with an increased risk also observed in South Asians, East Asians and other non-white groups, compared with white individuals. Black, East Asian, South Asian and Hispanic individuals with SLE tend to develop more severe disease with a greater number of manifestations and accumulate damage from lupus more rapidly. Increased genetic risk burden in these populations, associated with increased autoantibody reactivity in non-white individuals with SLE, may explain the more severe lupus phenotype. Even after taking into account socio-economic factors, race/ethnicity remains a key determinant of poor outcome, such as end-stage renal failure and mortality, in SLE. Community measures to expedite diagnosis through increased awareness in at-risk racial/ethnic populations and ethnically personalized treatment algorithms may help in future to improve long-term outcomes in SLE. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Renal-protective and ameliorating impacts of omega-3 fatty acids against aspartame damaged MDCK cells.

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Pandurangan, Muthuraman; Enkhtaivan, Gansukh; Veerappan, Muthuviveganandavel; Mistry, Bhupendra; Patel, Rahul; Moon, So Hyun; Nagajyothi, Patnamsetty Chidanandha; Kim, Doo Hwan

2017-11-01

Aspartame is widely used artificial sweeteners as food additives. Several researchers have pointed that the controversial report on the use of aspartame over more than decades. Omega-3 fatty acids are essential and unsaturated fatty acids, and it plays a remarkable role in vision, intelligence, neural development, and metabolism of neurotransmitters. Therefore, the present study was aimed to investigate the effect of omega-3 fatty acids on aspartame treated renal cells. Experimental groups were divided into three such as sham control, aspartame treated, and aspartame with omega-3 fatty acids. Cell viability was determined by sulforhodamine-b assay and flow cytometric analysis. The experimental results showed that the aspartame induced altered cell viability were reduced following treatment of aspartame with omega-3 fatty acids. Altered cell morphology was recovered by omega-3 fatty acids. DNA damage appeared in the highest concentration of aspartame used in this study. DNA damage characteristics such as comet tail and tiny head sections did not appear in the omega-3 fatty acids treated cells. Several microvilli and vesicular structures were found in aspartame treated cells. Altered morphology such as rounding, microvilli, and formation of dome-like structures did not appear in the omega-3 fatty acids with aspartame treated cells. Caspase-3 mRNA and protein expression were increased in aspartame treated cells, and these levels were reduced following omega-3 fatty acids treatment. Taking all these data together, it is suggested that the omega-3 fatty acids may be a therapeutic agent to reduce the aspartame induced biochemical and morphological alterations in normal renal cells. © 2017 BioFactors, 43(6):847-857, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Prolonged Pulmonary Exposure to Diesel Exhaust Particles Exacerbates Renal Oxidative Stress, Inflammation and DNA Damage in Mice with Adenine-Induced Chronic Renal Failure.

Science.gov (United States)

Nemmar, Abderrahim; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Hamadi, Naserddine Kamel; Ali, Badreldin H

2016-01-01

Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood. Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured. While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP. Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort.

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Pons-Estel, Guillermo J; González, Luis A; Zhang, Jie; Burgos, Paula I; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

2009-07-01

To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean +/- S.D. total disease duration of 6.6 +/- 3.6 years. Nearly 90% of the patients were women with a mean +/- s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94). Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.

Evaluation of extent of UTI related renal parenchymal damage in pediatric patient population

International Nuclear Information System (INIS)

Sharma, A.R.; Charan, S.; Silva, I.

2004-01-01

Introduction: Urinary tract infection (UTI) is important cause of morbidity in childhood. UTI may lead to involvement of renal parenchyma ranging from recoverable acute inflammation, renal scarring of Reflux nephropathy, hypertension and ultimately end stage renal disease. Hence, extent of renal parenchymal involvement bears prognostic significance in pediatric population. Laboratory and clinical parameters have inherent limitations in detecting and localizing renal parenchymal involvement in the settings of UTI. Objectives: The present study has been designed with the aim to determine the frequency and degree of renal parenchymal involvement in pediatric patients having urinary tract infection. MATERIALS AND METHODS: From May to December 2003, 33 consecutive children (65 Kidneys, 32-paired, I-solitary) aged one month to 12 years (mean age 3 years, 20M, 13F) with positive past history and culture documented urinary tract infection were enrolled in the study. They were subjected to Renal cortical scan using Tc-99m DMSA (20-100 MBq) on Dual detectors gamma camera (e.cam) fitted with LEHR collimator in anterior, posterior and posterior oblique projections. DMSA renal scans were interpreted as per Clarke's interpretation criteria. Renal ultrasound (RUS) and cystourethrogram (MCUG) were available in all the cases. Results: As per Clarke's classification, there were 19 children with no evidence of renal cortical involvement (Type-1). Renal parenchymal involvement found to be unilateral (Type-4 to Type-6) and bilateral (Type-7 and 8) in 8 and 6 children respectively. DMSA scan was abnormal in 20 of 65 kidneys (31%). MCUG was positive for presence of VUR in 34 kidneys (Group A) and negative for VUR in remaining 31 units (Group B). In Gp A, 18 of 34 kidneys (53%) showed renal parenchymal involvement on DMSA Scan. In Gp A, presence or absence of renal parenchymal damage on DMSA scan did not show any statistically significant difference in age, sex and grade of VUR. Whereas

Outcomes of 847 childhood-onset systemic lupus erythematosus patients in three age groups.

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Lopes, S R M; Gormezano, N W S; Gomes, R C; Aikawa, N E; Pereira, R M R; Terreri, M T; Magalhães, C S; Ferreira, J C; Okuda, E M; Sakamoto, A P; Sallum, A M E; Appenzeller, S; Ferriani, V P L; Barbosa, C M; Lotufo, S; Jesus, A A; Andrade, L E C; Campos, L M A; Bonfá, E; Silva, C A

2017-08-01

Objective The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0-9) vs 0 (0-6) vs 0 (0-7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups ( p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity.

Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage.

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Oberbauer, R

2008-12-01

Currently, the identification and validation of biomarkers of kidney injury is among the top priorities of many diagnostic biotechnology companies as well as academic research institutes. Specifically, in renal transplantation, validated biomarkers of tissue injury with good discriminatory power between the various renal compartments and the underlying pathophysiology are desired, because sequential allograft biopsies are limited in number and cannot be used as a screening tool. Given the high demands on these markers, it is not surprising that none of those currently under evaluation has been thoroughly validated for a specific entity. Published biomarker candidates for early tubular damage include neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance phase of renal transplantation. Given the complex prerequisites, it is not surprising that no biomarker panel has been sufficiently validated for clinical use. However, in the near future a biomarker for use as an indicator of renal tubule cell injury will be available. Troponin T or transaminase of the kidney may then at least be used to differentiate between functional renal failure (equivalent to a rise in creatinine) and intrinsic kidney injury.

The Sarawak lupus cohort: clinical features and disease patterns of 633 SLE patients in a single tertiary centre from East Malaysia.

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Teh, C L; Ling, G R; Aishah, Wan Sharifah

2015-01-01

Systemic lupus erythematosus (SLE) has been well studied in West Malaysian populations but lacking in East Malaysian populations. The aim of this study was to examine the clinical features and disease patterns of patients with SLE in a multiethnic East Malaysian population in Sarawak. All SLE patients who were treated in Sarawak General Hospital were reviewed in a retrospective longitudinal study using a standard protocol from 1 January 2006 to 31 December 2013. There were a total of 633 patients in our study with the female to male ratio of 12:1. Our study patients were of multiethnic origins with predominant Chinese ethnic group. They had a mean age of 36.9 ± 13.2 years and a mean duration of illness of 7.2 ± 6.0 years. The main involvements were haematological (74.2 %), malar rash (64.0 %) and renal (58.6 %). Chinese patients were less likely to have discoid lupus, pleuritis and pericarditis, while Malay patients were more likely to have arthritis. Bidayuh patients were more likely to have oral ulcer. Secondary antiphospholipid syndrome was more common in Chinese. The majority of patients were in clinical remission with low SDI. There were 58 deaths (9.2 %) during 2006-2013 with the main causes of death being flare of disease and infection.

Tuberculosis and systemic lupus erythematosus: a case-control study in Mexico City.

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Torres-González, Pedro; Romero-Díaz, Juanita; Cervera-Hernández, Miguel Enrique; Ocampo-Torres, Mario; Chaires-Garza, Luis Gerardo; Lastiri-González, Ernesto Alejandro; Atisha-Fregoso, Yemil; Bobadilla-Del-Valle, Miriam; Ponce-de-León, Alfredo; Sifuentes-Osornio, José

2018-04-20

To determine, among systemic lupus erythematosus patients, factors associated with active tuberculosis. We performed a case-control study, in a tertiary-care center in Mexico City. We defined cases as systemic lupus erythematosus patients with active tuberculosis and matched them 1:1 with systemic lupus erythematosus patients without tuberculosis (controls) by age, date of systemic lupus erythematosus diagnosis, and disease duration. We analyzed clinical variables, lupus disease activity (SLEDAI-2K), and accumulated damage (SLICC/ARC-DI). We performed a nonconditional logistic regression to determine factors associated with tuberculosis. We identified 72 tuberculosis cases among systemic lupus erythematosus patients, 58% were culture confirmed. Thirty-three percent (24/72) were pulmonary only, 47.2% (34/72) extrapulmonary only, and 19.4% both. After adjustment for age, gender, and socioeconomic status, SLEDAI-2K and SLICC/ARC-DI, a 1-year cumulative dose of prednisone ≥ 3 g (odds ratios (OR), 18.85; 95% confidence interval (95% CI), 6.91-51.45) was associated with tuberculosis, and the antimalarial treatment was protective (OR, 0.13; 95% CI, 0.04-0.36). Among systemic lupus erythematosus patients, cumulative dose of prednisone is associated with tuberculosis. Further research is required to elucidate the protective effect of antimalarial drugs for tuberculosis. Preventive strategies must be implemented in patients at risk.

Discoid Lupus Erythematosus

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... Name: Category: Share: Yes No, Keep Private Discoid Lupus Erythematosus Share | Discoid lupus erythematosus (DLE) is a chronic skin condition of ... occur. A small percentage of patients with discoid lupus can develop disease of the internal organs, which ...

Renal deterioration caused by carcinogens as a consequence of free radical mediated tissue damage: a review of the protective action of melatonin

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Gultekin, Fatih; Hicyilmaz, Hicran [Suleyman Demirel University, School of Medicine, Department of Biochemistry, Isparta (Turkey)

2007-10-15

This brief review summarizes some of the publications that document the preventive role of melatonin in kidney damage caused by carcinogens such as 2-nitropropane, arsenic, carbon tetrachloride, nitrilotriacetic acid and potassium bromate. Numerous chemicals generate excessive free radicals that eventually induce renal worsening. Melatonin partially or totally prevents free radical mediated tissue damages induced by many carcinogens. Protective actions of melatonin against the harmful effects of carcinogens are believed to stem from its direct free radical scavenging and indirect antioxidant activities. Dietary or pharmacologically given melatonin may attenuate the oxidative stress, thereby mitigating the subsequent renal damage. (orig.)

Reliability of the SF-36 in Japanese patients with systemic lupus erythematosus and its associations with disease activity and damage: a two-consecutive year prospective study.

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Baba, S; Katsumata, Y; Okamoto, Y; Kawaguchi, Y; Hanaoka, M; Kawasumi, H; Yamanaka, H

2018-03-01

We aimed to validate the reliability of the Medical Outcomes Study Short Form-36 (SF-36) among Japanese patients with systemic lupus erythematosus (SLE). Japanese patients with SLE ( n = 233) completed the SF-36 and other related demographic questionnaires, and physicians simultaneously completed the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Patients were prospectively followed for a repeat assessment the following year. The SF-36 subscales demonstrated acceptable internal consistency (Cronbach's α of 0.85-0.89), and an overall good test-retest reliability (intraclass correlation coefficient >0.70). The average baseline SF-36 subscale/summary scores except for "bodily pain" were significantly lower than those of the Japanese general population ( p 36 subscale/summary scores except for "vitality" and "mental component summary" at baseline, whereas the SLEDAI-2K did not. In the second year, "social functioning" and "mental component summary" of the SF-36 deteriorated among patients whose SDI or SLEDAI-2K score increased (effect sizes 36 demonstrated acceptable reliability among Japanese patients with SLE. Health-related quality of life measured by the SF-36 was reduced in Japanese patients with SLE and associated with disease damage, rather than disease activity.

Bilateral acute lupus pneumonitis in a case of rhupus syndrome

Directory of Open Access Journals (Sweden)

Supriya Sarkar

2012-01-01

Full Text Available Rhupus syndrome, the overlap of rheumatoid arthritis (RA and systemic lupus erythematosus (SLE, is an extremely uncommon condition. Organ damages found due to SLE are usually mild in rhupus. Lupus pneumonitis in rhupus syndrome has not been reported worldwide. We are reporting a 23-year-old female with bilateral symmetric erosive arthritis, oral ulcer, alopecia, polyserositis, anemia, leucopenia, positive RA-factor, anti nuclear antibody (ANA and anti ds-DNA. She presented with acute onset dyspnea, high fever, chest pain, tachycardia, tachypnea, hypoxia and respiratory alkalosis. High resolution computed tomography (HRCT-thorax showed bilateral, basal consolidation with air bronchogram. Repeated sputum and single broncho alveolar lavage (BAL fluid examination revealed no organism or Hemosiderin-laden macrophage. The diagnosis of rhupus was confirmed by combined manifestations of RA and SLE, and the diagnosis of acute lupus pneumonitis was established by clinico-radiological picture and by excluding other possibilities.

Children & Teens (with Lupus)

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... nine. blog Lupus at school: A guide for parents and kids Advice for communicating with your child's school about their lupus and ... teens on adjusting to life with lupus For teens, living with lupus can require some major ... in school Advice from parents and education experts on 504 and Individualized Education ...

77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

Science.gov (United States)

2012-06-27

...] Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical... ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment... of medical products for the treatment of lupus nephritis. Dated: June 22, 2012. Leslie Kux, Assistant...

Nocturnal and Circadian Rhythm of Blood Pressure Is Associated with Renal Structure Damage and Function in Patients with IgAN.

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Lin, Lirong; Zhang, Huhai; Yang, Jurong; Zhang, Jianguo; Li, Kailong; Huo, Bengang; Dai, Huanzi; Zhang, Weiwei; Yang, Jie; Tan, Wei; He, Yani

2016-01-01

Abnormal circadian rhythm of blood pressure (BP) is closely related to target organ damage in hypertension. However, the association between abnormal circadian rhythm of BP and renal injury is not clear. We investigated whether renal injury is associated with nocturnal BP and circadian rhythm of BP in Chinese IgAN patients. Clinic and 24 h ambulatory BP monitoring data were obtained from 330 Chinese IgAN patients with mean 24 h BP circadian BP, and 27% had nocturnal hypertension with a nondipping pattern. Compared with nocturnal normotensive patients, patients with nocturnal hypertension had significantly higher levels of blood cystatin C, blood uric acid, and lower estimated glomerular filtration rate (eGFR), and significantly a higher mean renal tissue injury score. The nondipping hypertensive group had significantly higher nocturnal diastolic and systolic BP, blood uric acid, and glomerulosclerosis rates, whereas eGFR was lower. In nondipping hypertensive patients, urinary sodium excretion and renal tissue injury scores were significantly higher than dipping patients. Nocturnal hypertension and abnormal circadian BP correlated with renal tissue injury, renal interstitial fibrosis, and aortic arch atherosclerosis. Abnormal circadian rhythm of BP and nocturnal hypertension are common clinical manifestations in Chinese IgAN patients with normal mean 24 h BP. Abnormal circadian BP and nocturnal hypertension may accelerate IgAN progression by inducing renal dysfunction and histopathological damage. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population.

Science.gov (United States)

Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

2015-12-01

The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population.A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group).Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model.Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population.

Relationship between health-related quality of life, disease activity and disease damage in a prospective international multicenter cohort of childhood onset systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Moorthy, L N; Baldino, M E; Kurra, V

2017-01-01

disease activity and damage. The multinational cohort ( n = 467) had relatively low disease activity and damage. Patient and parent HRQOL scores were significantly correlated. Asian and European patients had the highest HRQOL, while South and North American patients had lower HRQOL scores. Renal, CNS...

Obesity and renal hemodynamics

NARCIS (Netherlands)

Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.

2006-01-01

Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

Relation between myocardial damage and disease activity in patients with systemic lupus erythematosus by exercise {sup 201}Tl scintigraphy

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Kuzumoto, Masayuki [Nara Medical Univ. (Japan)

1997-08-01

Myocardial damage in patients with systemic lupus erythematosus (SLE) was evaluated using exercise thallium-201 myocardial scintigraphy, and the relationship between myocardial damage and disease activity of SLE was examined. Twenty-seven patients (26 women and 1 man, mean age 43 years), in whom extramural coronary artery lesions were excluded by coronary angiogram or presumed to be excluded by exercise electrocardiogram, were enrolled in this study. The mean duration of disease and the mean duration of corticosteroid therapy in these patients were 94 and 77 months, respectively. Exercise thallium-201 scintigraphy was performed twice (mean interval, 30 months) to evaluate the progression of myocardial damage. Myocardial ischemia as an index of myocardial damage was evaluated by visual analysis and ischemic score (IS). The changes in myocardial ischemia were categorized into 3 groups: improved, unchanged or worsened. The disease activity of SLE was determined by the SLE Disease Activity Index (SLEDAI), and the changes in this index were classified into the same three categories, as evaluated every six months between the two scintigraphic examinations. Disease activity was significantly correlated with myocardial ischemia (p<0.05), and with myocardial ischemia as diagnosed by {Delta}IS (difference in ischemic score between the first and second thallium-201 scintigrams: p<0.005). But neither the duration of disease nor the duration of corticosteroid therapy was correlated with IS at the first scintigraphy. These results indicate that control of SLE disease activity may be critical in the treatment of myocardial damage resulting from vascular lesions, especially intramyocardial small-artery disease, in patients with SLE. (author)

Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Science.gov (United States)

Závada, J; Sinikka Pesicková, S; Rysavá, R; Horák, P; Hrncír, Z; Lukác, J; Rovensky, J; Vítová, J; Havrda, M; Rychlík, I; Böhmova, J; Vlasáková, V; Slatinská, J; Zadrazil, J; Olejárová, M; Tegzova, D; Tesar, V

2014-01-01

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

Management of systemic lupus erythematosus during pregnancy: challenges and solutions

Directory of Open Access Journals (Sweden)

Knight CL

2017-03-01

Full Text Available Caroline L Knight, Catherine Nelson-Piercy Division of Women’s Health, Women’s Health Academic Centre, King’s College London and King’s Health Partners, St Thomas’ Hospital, London, UK Abstract: Systemic lupus erythematosus (SLE is a chronic, multisystem autoimmune disease predominantly affecting women, particularly those of childbearing age. SLE provides challenges in the prepregnancy, antenatal, intrapartum, and postpartum periods for these women, and for the medical, obstetric, and midwifery teams who provide their care. As with many medical conditions in pregnancy, the best maternal and fetal–neonatal outcomes are obtained with a planned pregnancy and a cohesive multidisciplinary approach. Effective prepregnancy risk assessment and counseling includes exploration of factors for poor pregnancy outcome, discussion of risks, and appropriate planning for pregnancy, with consideration of discussion of relative contraindications to pregnancy. In pregnancy, early referral for hospital-coordinated care, involvement of obstetricians and rheumatologists (and other specialists as required, an individual management plan, regular reviews, and early recognition of flares and complications are all important. Women are at risk of lupus flares, worsening renal impairment, onset of or worsening hypertension, preeclampsia, and/or venous thromboembolism, and miscarriage, intrauterine growth restriction, preterm delivery, and/or neonatal lupus syndrome (congenital heart block or neonatal lupus erythematosus. A cesarean section may be required in certain obstetric contexts (such as urgent preterm delivery for maternal and/or fetal well-being, but vaginal birth should be the aim for the majority of women. Postnatally, an ongoing individual management plan remains important, with neonatal management where necessary and rheumatology follow-up. This article explores the challenges at each stage of pregnancy, discusses the effect of SLE on pregnancy and

Comparison of renal artery, soft tissue, and nerve damage after irrigated versus nonirrigated radiofrequency ablation.

Science.gov (United States)

Sakakura, Kenichi; Ladich, Elena; Fuimaono, Kristine; Grunewald, Debby; O'Fallon, Patrick; Spognardi, Anna-Maria; Markham, Peter; Otsuka, Fumiyuki; Yahagi, Kazuyuki; Shen, Kai; Kolodgie, Frank D; Joner, Michael; Virmani, Renu

2015-01-01

The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group (Pradiofrequency group (Pradiofrequency group and conventional radiofrequency group (P=0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater (Pradiofrequency ablation, and there is a trend toward less nerve damage. © 2014 American Heart Association, Inc.

Urinary excretion of furosemide in rats with HgCl sub 2 -induced acute renal damage

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Fujimura, Akio; Sudoh, Toshiaki; Ohashi, Kyoichi; Ebihara, Akio (Jichi Medical School, Tochigi (Japan))

1992-01-01

To examine the influence of mercuric chloride (HgCl{sub 2})-induced acute renal damage on urinary excretion of furosemide, HgCl{sub 2} or its vehicle along was given intraperitoneally to Wistar rats. The following two experiments were done. Study 1: three percent body weight (b.w.) of 1% NaCl solution or furosemide in 3% b.w. of 1% NaCl solution was given orally before and after HgCl{sub 2} treatment, and an 8-hour urine was collected. Study 2: furosemide was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-{beta}-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl{sub 2}-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl{sub 2} were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl{sub 2}-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl{sub 2}-induced acute renal damage.

Lupus anticoagulants and antiphospholipid antibodies

Science.gov (United States)

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Identification and treatment of APS renal involvement.

Science.gov (United States)

Tektonidou, M G

2014-10-01

Renal involvement in antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-related APS, includes renal artery stenosis or thrombosis, renal infarction, renal vein thrombosis and a small-vessel vaso-occlusive nephropathy defined as "antiphospholipid antibody (aPL)-associated nephropathy." aPL-associated nephropathy is characterized by acute lesions, thrombotic microangiopathy, and chronic lesions such as fibrous intimal hyperplasia, organizing thrombi with or without recanalization, fibrous occlusions of arteries or arterioles and focal cortical atrophy. Systemic hypertension, hematuria, proteinuria (ranging from mild to nephrotic level) and renal insufficiency represent the major clinical manifestations associated with aPL-associated nephropathy. Similar renal histologic and clinical characteristics have been described among all different groups of patients with positive aPL (primary APS, SLE-related APS, catastrophic APS and SLE/non-APS with positive aPL). In patients with aPL-associated nephropathy lesions in the absence of other causes associated with similar histological characteristics, aPL testing needs to be considered. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Predicting long-term renal damage in children with vesicoureteral reflux under conservative initial management: 205 cases in a tertiary referral center.

Science.gov (United States)

Alvarez, Natalia; Alvira, Reyes Delgado; Ruiz, Yurema Gonzalez; Atuan, Rafael Fernandez; Hinojosa, Alexander Siles; Heras, Miguel Angel Rihuete; Roldan, Marisa Justa; Romero, Jesus Gracia

2018-01-01

Vesicoureteral reflux (VUR) is one of the most common ailments in children. Evidence-based guidelines recommend conservative treatment in children with VUR, followed by endoscopic surgery in those with breakthrough febrile urinary tract infections (UTIs). Despite this fact, the management of VUR is still controversial. Our objective is to evaluate the conservative strategy in children with primary VUR in terms of renal function and scarring, and identify factors associated with poor prognosis in those children. A retrospective study was carried out in a tertiary center in children with primary VUR under conservative strategy treatment from 1989 to 2015. Data extracted included age of presentation, family and prenatal backgrounds, radiographic evaluation including ultrasound (US), dimercaptosuccinic acid (DMSA) scans and voiding cystourethrogram (VCUG). The SPSS program was used for statistical analysis. Two-hundred and five patients were diagnosed and followed a conservative therapy scheme (49.8% males, 50.2% females) after febrile UTI (73.17%) or prenatal diagnosis (26.83%). VCUG showed 53.20% of low-moderate VUR grade, 46.80% high VUR grade. Renal damage was present at diagnosis in 40.89%. Mean follow-up reakthrough recurrent febrile UTIs and underwent surgery. Conservative therapy was followed in 189 patients. Renal scarring or decreased kidney function were shown in 15.12% respectively. Renal damage was identified as a risk factor for poor prognosis (p-value Conservative strategy is a feasible treatment for primary VUR in children. The majority of cases could be managed conservatively with good outcomes after long-term follow-up. Decreased renal function is more frequent in patients with high-grade VUR. Renal damage at diagnosis increases the risk for surgical treatment.

IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus

Science.gov (United States)

Zhao, Ming; Zhou, Yin; Zhu, Bochen; Wan, Mengjie; Jiang, Tingting; Tan, Qiqun; Liu, Yan; Jiang, Juqing; Luo, Shuaihantian; Tan, Yixin; Wu, Haijing; Renauer, Paul; Gutiérrez, Maria del Mar Ayala; Palma, Maria Jesús Castillo; Castro, Rafaela Ortega; Fernández-Roldán, Concepción; Raya, Enrique; Faria, Raquel; Carvalho, Claudia; Alarcón-Riquelme, Marta E; Xiang, Zhongyuan; Chen, Jinwei; Li, Fen; Ling, Guanghui; Zhao, Hongjun; Liao, Xiangping; Lin, Youkun; Sawalha, Amr H; Lu, Qianjin

2016-01-01

Objective Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. Methods IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren’s syndrome (pSS) were used for validation. Results Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. Conclusions The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE. PMID:26787370

Lupus Nephritis

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... in men and most often strikes during the child-bearing years. Nine out of 10 people who have lupus are women. Lupus is also more common in people of African or Asian background. African Americans and Asian Americans ...

ENDOCARDITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

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AMEL Harzallah

2017-04-01

Full Text Available Endocarditis is one of the most prevalent forms of cardiac involvement in patients with lupus, as it is considered as one a life-threatening complication. Libman-Sacks endocarditis is common. Infective endocarditis can also cause complications within immunocompromised patients. The aim of this study is to determine particularities of endocarditis in patients with lupus and to look for distinguishing features between infectious or immunological origin. A retrospective study was conducted on patients with lupus presenting endocarditis. Lupus was diagnosed according to the American college of rheumatology criteria. The diagnosis of endocarditis was made based on the modified Duke criteria. The present case report studies seven cases of endocarditis. Six of these patients are women and the other one is a man. They are aged meanly of 29.4 years (extremes: 20-36. Fever was present in all the cases with a new cardiac murmur in six cases and a modification of its intensity in one case. Biologic inflammatory syndrome was present in six cases. Cardiac ultrasound performed in six cases made the diagnosis of endocarditis which involved the left heart valves in five cases and the right heart valves in one case. Valvular insufficiency was identified in six patients. The valve involvement was mitral in two cases, mitro-aortic in two others, aortic in the fifth one and tricuspid in the sixth one. Endocarditis was infectious in 4 cases, thanks to positive blood culture. The germs identified were gram negative bacilli in two cases, anaerobic organism in one case and gram positive cocci in one case. Candida albicans was isolated in one case. Libman-Sacks endocarditis was objectified in three cases. A combination of Libman-Sacks endocarditis with infectious endocarditis was diagnosed in one case. The treatment consisted of antibiotics in four cases with surgery in two cases. The outcome was favorable in five cases and fatal in the two others. Endocarditis in lupus

Effects of chronic fructose overload on renal dopaminergic system: alteration of urinary L-dopa/dopamine index correlates to hypertension and precedes kidney structural damage.

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Rukavina Mikusic, Natalia L; Kouyoumdzian, Nicolás M; Del Mauro, Julieta S; Cao, Gabriel; Trida, Verónica; Gironacci, Mariela M; Puyó, Ana M; Toblli, Jorge E; Fernández, Belisario E; Choi, Marcelo R

2018-01-01

Insulin resistance induced by a high-fructose diet has been associated to hypertension and renal damage. The aim of this work was to assess alterations in the urinary L-dopa/dopamine ratio over three time periods in rats with insulin resistance induced by fructose overload and its correlation with blood pressure levels and the presence of microalbuminuria and reduced nephrin expression as markers of renal structural damage. Male Sprague-Dawley rats were randomly divided into six groups: control (C) (C4, C8 and C12) with tap water to drink and fructose-overloaded (FO) rats (FO4, FO8 and FO12) with a fructose solution (10% w/v) to drink for 4, 8 and 12 weeks. A significant increase of the urinary L-dopa/dopamine ratio was found in FO rats since week 4, which positively correlated to the development of hypertension and preceded in time the onset of microalbuminuria and reduced nephrin expression observed on week 12 of treatment. The alteration of this ratio was associated to an impairment of the renal dopaminergic system, evidenced by a reduction in renal dopamine transporters and dopamine D1 receptor expression, leading to an overexpression and overactivation of the enzyme Na + , K + -ATPase with sodium retention. In conclusion, urinary L-dopa/dopamine ratio alteration in rats with fructose overload positively correlated to the development of hypertension and preceded in time the onset of renal structural damage. This is the first study to propose the use of the urinary L-dopa/dopamine index as marker of renal dysfunction that temporarily precedes kidney structural damage induced by fructose overload. Copyright © 2017 Elsevier Inc. All rights reserved.

[Systemic lupus erythematodes].

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Lukác, J; Rovenský, J; Lukácová, O; Kozáková, D

2006-01-01

Systemic lupus erythematodes (SLE) is chronic autoimmune disease, characteristic by production of autoantibodies against different autoantigens. Etiopathogenesis in not precise determinated, but genetic, immunologic, hormonal factors or influence of environment are assumed. It manifests by various symptoms and it can affect whichever organ or system in the body. Clinical manifestation are due chronic inflammation in the tissues, which is caused first of all by deposit of immunocomplex and by cytotoxic damage. At the last decades the mortality of patients with SLE is markly lower and their live is prolong. In spite of this diagnostic, to follow up and therapy of this disease is complicated and it requires the colaboration of more branches of medicine.

The valuation of 99Tcm-DMSA renal cortical scintigraphy for prediction of renal scarring in children with acute pyelonephritis

International Nuclear Information System (INIS)

Zhao Ruifang; Ji Zhiying; Lv Xiaomei; Wu Ha; Li Yiwei; Gu Fanlei; Zhao Xiaofei

2009-01-01

Objective: Acute pyelonephritis (APN) is a common infectious disease in childhood. APN may result in ineversible renal scarring. 99 Tc m -dimercaptsuccinic (DMSA) renal cortical scintigraphy was reported to be highly sensitive and specific for detection APN and renal scarring. The aim of this study was to determine the incidence of renal scarring in a group of children with APN and to evaluate the relative factors at risk of scarring using 99 Tc m -DMSA renal cortical scintigraphy. Methods: One hundred and eighteen patients (44 males, 74 females, age range: 1 month to 14 years) with APN underwent DMSA renal cortical scan before treatment and six month after treatment to identify renal damage and renal scarring. The degree of renal damage was divided to grade I to IV. A directed radionuclide cystography (DRC) was performed in 72 cases to evaluate vesicoureteric reflux (VUR). Statistical analysis between all those relative factors was performed using Spearman grading relational analysis. The software was SPSS 11.5. Results: The follow-up renal cortical scan revealed that 79 normal kidneys on first scan remained normal; of 64 kidneys with grade I damage, 7.81% (5/64) developed renal scar; of 51 kidneys with grade II, 49.02% (25/51) developed renal scar; of 19 with grade III, 68.42% (13/19) developed renal scar; of 23 with grade IV, 100.00% (23/23) developed renal scar. There was a significant relationship between the incidence of renal scar on follow-up and the grade of renal damage on first scan (r=0.877, P<0.01). VUR was found in 54.17% (78/144) per renal unit. Only 4.55% (3/66) of those with non-refluxing ureters developed renal scars on follow-up. One of four patients with mild-refluxing ureters developed renal scars. 46.51% (20/43) of those with moderate-refluxing ureters developed renal scars. 87.10% (27/31) of those with severe-refluxing ureters developed renal scars. There was a significant relationship between the incidence of renal scarring in follow-up and

The endothelial deprotection hypothesis for lupus pathogenesis: the dual role of C1q as a mediator of clearance and regulator of endothelial permeability [v1; ref status: indexed, http://f1000r.es/50o

Directory of Open Access Journals (Sweden)

József Prechl

2015-01-01

Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous multifactorial systemic autoimmune disease affecting several organs. SLE can start relatively early in life and results in impaired quality of life and shortened life expectancy because of a gradual disease progression leading to cardiovascular, renal and neoplastic disease. The basic mechanisms of the pathogenesis of the disease still remain to be clarified. It is clear that complement proteins play a key and complex role in the development of SLE. Complement component C1q has been known to be a fundamental component of lupus development, but most explanations focus on its role in apoptotic debris removal. Importantly, C1q was recently found to play a key role in the maintenance of vascular endothelial integrity. We suggest that apoptotic products, endothelial cells and extracellular matrix components, which display negatively charged moieties, compete for binding to molecules of the innate humoral immune response, like C1q. Genetic or acquired factors leading to an increased load of apoptotic cell debris and decrease or absence of C1q therefore interfere with the regulation of endothelial permeability and integrity. Furthermore, we suggest that lupus is the net result of an imbalance between the two functions of immune clearance and vascular endothelial integrity maintenance, an imbalance triggered and sustained by autoimmunity, which skews C1q consumption by IgG-mediated complement classical pathway activation on autoantigens. In this triangle of innate clearance, autoimmunity and endothelial integrity, C1q plays a central role. Hence, we interpret the pathogenesis of lupus by identifying three key components, namely innate immune clearance, autoimmunity and endothelial integrity and we establish a link between these components based on the protective role that innate clearance molecules play in endothelial renewal. By including the vasoprotective role of C1q in the interpretation of SLE

Metabolic syndrome in Iranian patients with systemic lupus erythematosus and its determinants.

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Fatemi, Alimohammad; Ghanbarian, Azadeh; Sayedbonakdar, Zahra; Kazemi, Mehdi; Smiley, Abbas

2018-01-05

The aim of this study was to determine the prevalence of metabolic syndrome (MetS) in Iranian patients with systemic lupus erythematosus (SLE) and its determinants. In a cross-sectional study, 98 patients with SLE and 95 controls were enrolled. Prevalence of MetS was determined based on American Heart Association and National Heart, Lung, and Blood Institute (AHA/NHLBI) and 2009 harmonizing criteria. In addition, demographic features and lupus characteristics such as disease duration, pharmacological treatment, laboratory data, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index (SDI) were recorded. The predictors of MetS were obtained by backward stepwise regression analysis. Using AHA/NHLBI, MetS was observed in 35 (35.7%) patients and 28 (29.8%) controls (P = 0.4). Using harmonizing criteria, MetS was observed in 37 (37.7%) patients and 33 (35.1%) controls (P = 0.7). There was no difference in frequency distribution of MetS components between the patients and the controls. In multivariate regression analysis, low C3, blood urea nitrogen (BUN), and body mass index were independent determinants of MetS in lupus patients. BUN, low C3, and body mass index were the major determinants of MetS in lupus patients.

Nail fold Capillaroscopic Findings in Iranian Patients with Systemic Lupus Erythematosus

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Alireza Rajaei

2016-10-01

Full Text Available Background: Systemic Lupus Erythematosus is a progressive autoimmune disease with a wide range of morphological and functional changes in microscopic examination of small blood vessels. Identification of vascular diseases at early stage, plays an essential role in the prevention of its’ vascular complications. Nailfold capillaroscopy (NFC is a non-invasive, easy, painless, and accurate method for evaluation of microcirculation and could be used for this purpose. The vast majority of studies on capillaroscopy in lupus patients have shown that changes are not specified to lupus –unlike Systemic Sclerosis- and are more likely to overlap with other diseases. Therefore, it was decided to check capillaroscopic changes and evaluate morphological changes and capillary structure in terms of quality and quantity in lupus patients.Materials and Methods: Nail fold capillaroscopic findings of 114 patients aged 19-75 years old were reviewed in this study. The results were categorized as: a normal, b non-specific morphological abnormalities, and c Scleroderma-like pattern.  Results were analyzed qualitatively and quantitatively using SPSS 21 software. "Chi square" test was used to analyze the relationships between variables (P<0.05 was considered significant.Results: Our results show that Lupus –independent of any other microvascular risk factor can significantly affect the morphology and structure of blood circulation and these changes are shown with detail by nail fold capillaroscopy.Conclusion: Most of the findings are in line with similar studies performed by other investigators in this field. However, no specific pattern was recognized and microbleeding was higher in our patients with scleroderma-like pattern of involvement.

Systemic lupus erythematosus and thyroid disease - Experience in a single medical center in Taiwan.

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Liu, Yu-Chuan; Lin, Wen-Ya; Tsai, Ming-Chin; Fu, Lin-Shien

2017-06-28

To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement. Copyright © 2017. Published by Elsevier B.V.

Ficolins and the lectin pathway of complement in patients with systemic lupus erythematosus

DEFF Research Database (Denmark)

Hein, Estrid; Nielsen, Louise Aas; Nielsen, Christoffer T

2015-01-01

The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. EDTA plasma samples from 68 Danish SLE patients and 29 healthy...... Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC...

Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

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Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Thomale, Jürgen [Institute of Cell Biology, University Duisburg-Essen, 45122 Essen (Germany); Schupp, Nicole [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany)

2016-02-01

The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

International Nuclear Information System (INIS)

Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

2016-01-01

The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

Possible Protective Effect of Hydroxychloroquine on Retarding the Occurrence of Integument Damage in Lupus: Data from LUMINA, a Multiethnic Cohort

Science.gov (United States)

Pons-Estel, Guillermo J.; Alarcón, Graciela S.; González, Luis A.; Zhang, Jie; Vilá, Luis M.; Reveille, John D.; McGwin, Gerald

2010-01-01

Objective To determine the features predictive of time-to-integument damage in patients with systemic lupus erythematosus (SLE) from a multiethnic cohort (LUMINA). Methods SLE LUMINA patients (n=580), age ≥16 years, disease duration ≤5 years at baseline (T0), of African American, Hispanic and Caucasian ethnicity were studied. Integument damage was defined per the SLICC damage index (scarring alopecia, extensive skin scarring and skin ulcers lasting at least six months); factors associated with time-to-its occurrence were examined by Cox proportional univariable and multivariable (main model) hazards regression analyses. Two alternative models were also examined; in model 1 all patients, regardless of when integument damage occurred (n=94), were included; in model 2 a time-varying approach (GEE) was employed. Results Thirty-nine (6.7%) of 580 patients developed integument damage over a mean (SD) total disease duration of 5.9 (3.7) years and were included in the main multivariable regression model. After adjusting for discoid rash, nailfold infarcts, photosensitivity and Raynaud’s phenomenon (significant in the univariable analyses), disease activity over time [Hazard ratio (HR)=1.17; 95% Confidence interval (CI) 1.09–1.26)] was associated with a shorter time-to-integument damage whereas hydroxychloroquine use (HR=0.23, 95% CI 0.12–0.47) and Texan-Hispanic (HR=0.35; 95% CI 0.14–0.87) and Caucasian ethnicities (HR=0.37; 95% CI 0.14–0.99) were associated with a longer time. Results of the alternative models were consistent with those of the main model albeit in model 2 the association with hydroxychloroquine was not significant. Conclusions Our data indicate that hydroxychloroquine use is possibly associated with a delay in integument damage development in patients with SLE. PMID:20391486

Burden of lupus on work: Issues in the employment of individuals with lupus.

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Agarwal, Neelam; Kumar, Vinod

2016-10-17

Systemic lupus erythematosus (SLE) or Lupus is one of the leading causes of work disability in the United States, accounting for about 20% of the more than estimated 1.5 million Americans with a work disability. The symptoms of lupus can have a profound impact on the person's employment. Impacts of lupus are more pronounced among young and middle-adulthood. Studies have shown that loss in work hours cost the nation nearly $13 billion annually. The loss also impacts the individual's work, quality of life, self-management, and self-efficacy. In this article, the author describes the financial burden of lupus. The article also describes the substantial impact of lupus on employment outcomes for individuals living with the condition. The author also reviews major signs and symptoms of disease and their impact on employment. Findings from this research can be used to identify various accommodations and strategies for individuals to prevent flare-ups. The paper presents innovative strategies that include early interventions and how employers andco-workers can provide helpful support that includes job accommodations to individuals with lupus.

Urinary Beta-2Microglobulin: An Indicator of Renal Tubular Damage after Extracorporeal Shock Wave Lithotripsy.

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Nasseh, Hamidreza; Abdi, Sepideh; Roshani, Ali; Kazemnezhad, Ehsan

2016-12-08

This study aims to determine extracorporeal shock wave lithotripsy (ESWL)-induced renal tubular damageand the affecting factors by measuring urinary beta2microglobulin (β2M) excretion. This is a cross-sectional study conducted on 91 patients with renal stones who underwentESWL during 2012. Urinary beta2microglobulin was measured immediately before and after the procedure foreach patient and analyzed based on different variables to evaluate factors affecting ESWL-induced renal tubularinjury. Mean ± SD urinary beta2-microglobulin values, before and after ESWL were 0.08 ± 0.07 and 0.22 ± 0.71mg/dL respectively, the average difference between which was equal to 0.14 ± 0.07 mg/dL. These figures exhibiteda 166.66% rise in the urinary β2M concentration after ESWL which was statistically significant (P ESWL (P = .02) were predictive factors ofhigher post-ESWL urinary beta2-microglobulin excretion. Urinary excretion of beta2-microglobulin increased significantly immediately after ESWL. Thesechanges could indicate that ESWL is a contributing factor to renal tubular damage. It also seems that in patientswith hypertension and a previous history of ESWL the likelihood of this injury is higher than others.

The endothelial deprotection hypothesis for lupus pathogenesis: the dual role of C1q as a mediator of clearance and regulator of endothelial permeability [v2; ref status: indexed, http://f1000r.es/5d5

Directory of Open Access Journals (Sweden)

József Prechl

2015-05-01

Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous multifactorial systemic autoimmune disease affecting several organs. SLE can start relatively early in life and results in impaired quality of life and shortened life expectancy because of a gradual disease progression leading to cardiovascular, renal and neoplastic disease. The basic mechanisms of the pathogenesis of the disease still remain to be clarified. It is clear that complement proteins play a key and complex role in the development of SLE. Complement component C1q has been known to be a fundamental component of lupus development, but most explanations focus on its role in apoptotic debris removal. Importantly, C1q was recently found to play a key role in the maintenance of vascular endothelial integrity. We suggest that apoptotic products, endothelial cells and extracellular matrix components, which display negatively charged moieties, compete for binding to molecules of the innate humoral immune response, like C1q. Genetic or acquired factors leading to an increased load of apoptotic cell debris and decrease or absence of C1q therefore interfere with the regulation of endothelial permeability and integrity. Furthermore, we suggest that lupus is the net result of an imbalance between the two functions of immune clearance and vascular endothelial integrity maintenance, an imbalance triggered and sustained by autoimmunity, which skews C1q consumption by IgG-mediated complement classical pathway activation on autoantigens. In this triangle of innate clearance, autoimmunity and endothelial integrity, C1q plays a central role. Hence, we interpret the pathogenesis of lupus by identifying three key components, namely innate immune clearance, autoimmunity and endothelial integrity and we establish a link between these components based on the protective role that innate clearance molecules play in endothelial renewal. By including the vasoprotective role of C1q in the interpretation of SLE

Anti-neutrophil cytoplasmic antibody negative crescentic paucimmune glomerulonephritis in a case of scleroderma with systemic lupus erythematosus overlap

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Rohit Tewari

2016-01-01

Full Text Available Renal Involvement in scleroderma is a known problem and the manifestations are well described. Renal involvement in systemic lupus erythematosus (SLE is also well known. However, in scleroderma and SLE overlap syndrome, the renal findings may vary being a combination of features of immune complex mediated glomerulonephritis as well as thrombotic microangiopathy. We report a case in which the renal manifestation in such a situation was of a focal necrotising pauci-immune glomerulonephritis with crescents, anti-neutrophil cytoplasmic antibody negative. To the best of our knowledge, such manifestations have not been described before. Renal dysfunction in a normotensive setting in such a case should direct one towards evaluation for other causes and should prompt a kidney biopsy. This would be valuable in delineating the pathological process in the kidney and would help in guiding therapy.

Lupus Foundation of America

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... Store Read About Our $3.8M Commitment to Stem Cell Research. Learn More Committed to Advancing Research on Lupus ... person with lupus? Get Answers Latest News & Stories Research News | Nov. 16, 2017 Major Lupus Stem Cell Study Receives Funding $3.8 million committed by ...

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review.

Science.gov (United States)

Costallat, Beatriz Lavras; Ferreira, Daniel Miranda; Lapa, Aline Tamires; Rittner, Letícia; Costallat, Lilian Tereza Lavras; Appenzeller, Simone

2018-01-01

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms "lupus", "systemic lupus erythematosus", "SLE", "diffusion tensor imaging", "DTI", "white matter" (WM), "microstructural damage", "tractography", and "fractional anisotropy"; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Cicatriz renal: factores de riesgo relacionados con infección urinaria Renal scar: risk factors related to urinary infection

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Lourdes María Pérez Clemente

2007-06-01

Full Text Available La infección urinaria es una de las infecciones bacterianas más frecuente en la niñez, superada solamente por las infecciones respiratorias. En algunos casos, puede causar cicatrices renales que pueden inducir complicaciones futuras, como la hipertensión arterial y enfermedad renal crónica. Los métodos de diagnóstico por imagen en los niños tienen como objetivo identificar a los pacientes en riesgo de desarrollar cicatrices renales o daño renal permanente, o de prevenir la progresión del daño renal preexistente. Se evaluaron retrospectivamente los datos clínicos de 100 niños con diagnóstico de infección urinaria, a los cuales se les realizó gammagrafía renal con ácido dimercaptosuccínico (DMSA. Se correlacionó la presencia de cicatriz renal con la edad, sexo, número de episodios de infección urinaria y presencia de reflujo vesicoureteral. Se demostró que todo niño con infección urinaria, independientemente del sexo, corre el riesgo de desarrollar cicatriz renal, el cual aumenta con la presencia de reflujo vesicoureteral, infecciones recurrentes y en la medida en que aumenta la edad. Por ello sugerimos estudiar, mediante ultrasonido, cistografía y gammagrafía con DMSA marcado con tecnecio 99 (Tc99m-DMSA, a todo niño con infección urinaria, para detectar oportunamente a quienes están en riesgo de desarrollar cicatriz renal o daño renal permanente.Urinary infection is one of the most common bacterial infections in childhood after respiratory infections. In some cases, it can cause renal scars that may lead to future complications like blood hypertension and chronic renal disease. The diagnostic imaging methods for children are aimed at identifying those patients at risk of developing renal scars or a permanent renal damage, and preventing the progression of pre-existing renal damage. Clinical data from 100 children diagnosed with urinary infection, who had been performed a renal DMSA scintigraphy, were retrospectively

Riesgo de daño renal cicatrizal después de infección del tracto urinario en recién nacidos Risk of cicatricial renal damage after urinary tract infection in newborns

Directory of Open Access Journals (Sweden)

Manuel Díaz Alvarez

2007-03-01

Full Text Available El presente trabajo se realizó con el objetivo de determinar la prevalencia de daño renal cicatrizal e identificar los factores de riesgo a él contribuyentes en niños recién nacidos con la primera infección del tracto urinario. Se llevó a cabo un estudio analítico de factores de riesgo, caso-control, con regresión logística binominal, en recién nacidos con infección del tracto urinario de localización alta, adquirida en la comunidad, que fueron ingresados consecutivamente en el Hospital Pediátrico Universitario «Juan M. Márquez», entre febrero de 1992 y diciembre de 2004. Se realizó gammagrafía renal con DMSA para identificar cicatrices renales. Las pruebas de chi cuadrado y regresión logística se aplicaron para identificar factores de riesgo independientes. La prevalencia de daño renal cicatrizal fue de 25,4 %. En el modelo de regresión se incluyeron para análisis multivariado los factores de riesgo: ultrasonido prenatal con pielectasia, microorganismo diferente de Escherichia coli, ultrasonido renal posnatal con anomalías, presencia de reflujo vesicoureteral de cualquier grado, reinfección en los primeros 3 meses de vida, sexo masculino, retardo en inicio del tratamiento antibiótico ≥ 4 d, leucocituria ≥ 10 000/mL, respuesta desfavorable al tratamiento inicial y bacteriemia al mismo microorganismo de la infección urinaria. Finalmente solo resultaron significativos (p The present paper was aimed at determining the prevalence of cicatricial renal damage and to identify the risk factors contributing to it in newborns with urinary tract infection for the first time. An analytical case-control study of the risk factors was conducted by binominal logistic regression in newborns with an upper urinary tract infection acquired in the community that were consecutively admitted in “ Juan Manuel Márquez” University Children Hospital from February 1992 to December 2004. A renal scintigraphy with DMSA was performed to

Role of MHC-Linked Susceptibility Genes in the Pathogenesis of Human and Murine Lupus

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Manfred Relle

2012-01-01

Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus.

Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM.

Science.gov (United States)

Paoletti, Ernesto; Bellino, Diego; Amidone, Marco; Rolla, Davide; Cannella, Giuseppe

2006-01-01

To date, few studies have used ambulatory pressure monitoring (ABPM) in patients with chronic kidney disease (CKD) before the start of dialysis treatment. The aim of this study was therefore to ascertain the correlates of arterial hypertension assessed by ABPM in CKD patients at their first referral to a nephrologist. We studied 244 (164 men; mean age 63 years) nondiabetic patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot) and sodium (UNa) excretion assessed using routine methods. According to ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives, 26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both lower CrCl (p=0.0033), and higher Uprot (p nighttime SBP > 24-hour PP > daytime PP > daytime SBP > 24-hour SBP. In CKD patients, proteinuria is the strongest correlate of arterial hypertension and particularly of increased nocturnal PP, possibly as an expression of vascular damage. On the basis of these results, ABPM appears to be the most reliable tool for detecting the associations between raised BP (particularly nighttime hypertension) and renal damage in CKD patients not yet on renal replacement therapy (RRT).

Protective Effect of Cleistocalyx nervosum var. paniala Fruit Extract against Oxidative Renal Damage Caused by Cadmium

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Warut Poontawee

2016-01-01

Full Text Available Cadmium nephrotoxicity is a serious environmental health problem as it will eventually end up with end stage renal disease. The pathobiochemical mechanism of this toxic heavy metal is related to oxidative stress. This study investigated whether Cleistocalyx nervosum var. paniala fruit extract (CNFE could protect the kidney against oxidative injury caused by cadmium. Initial analysis of the extract revealed antioxidant abilities and high levels of polyphenols, particularly catechin. Its potential renal benefits was further explored in rats treated with vehicle, CNFE, cadmium (2 mg/kg, and cadmium plus CNFE (0.5, 1, 2 g/kg for four weeks. Oxidative renal injury was developed after cadmium exposure as evidenced by blood urea nitrogen and creatinine retention, glomerular filtration reduction, renal structural damage, together with increased nitric oxide and malondialdehyde, but decreased antioxidant thiols, superoxide dismutase, and catalase in renal tissues. Cadmium-induced nephrotoxicity was diminished in rats supplemented with CNFE, particularly at the doses of 1 and 2 g/kg. It is concluded that CNFE is able to protect against the progression of cadmium nephrotoxicity, mostly via its antioxidant power. The results also point towards a promising role for this naturally-occurring antioxidant to combat other human disorders elicited by disruption of redox homeostasis.

Lupus nephritis in Lebanon.

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Uthman, I W; Muffarij, A A; Mudawar, W A; Nasr, F W; Masri, A F

2001-01-01

This is a retrospective study of the clinicopathological characteristics of 50 systemic lupus erythematosus patients with nephritis who underwent a kidney biopsy and were admitted to the American University of Beirut Medical Center, in Lebanon, between 1979 and 1999. There were 43 females and seven males, with a median age of 24 y. Renal histology slides from these patients were assessed according to the World Health Organization classification, and were distributed as follows: class I (n = 3, 6%); class II (n = 14, 28%); class III (n = 11, 22%); class IV (n = 19, 38%); class V (n = 1, 2%); class VI (n = 2, 4%). All the patients received oral prednisone, in addition the following treatments were used: pulse intravenous (i.v.) cyclophosphamide (n = 23, 46%); azathioprine (n = 22, 44%); pulse i.v. steroids (n = 19, 38%); chloroquine sulfate (n = 17, 34%); methotrexate (n = 5, 10%); and plasmapheresis (n = 2, 4%). The median duration of follow-up was 5 y (range 1-33 y). On their last evaluation, out of 37 patients who were followed, 20 patients (54%) had controlled disease, eight patients (22%) were still on active medical treatment, four patients (11%) were on chronic hemodialysis, and five patients (13%) had died. Unlike three other Arab populations studies from Kuwait, United Arab Emirates and Saudi Arabia, where the most frequent histopathologic abnormality was class III, diffuse proliferative LN (class IV) was the most common type of lupus nephritis in Lebanon, similarly to reports from USA, France, Netherlands, South Africa, Thailand and Taiwan.

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

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Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

2017-02-01

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia

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Chrispal A

2009-01-01

Full Text Available Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartter′s syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.

Lupus nephritis

African Journals Online (AJOL)

1991-03-02

Mar 2, 1991 ... A recent large Australian series! on lupus nephritis emphasises .... patent capillary lumina and thickened capillary walls. ... (Australia). 135. 27. 58. 15. This study (RSA). 51. 33. 63. 4 have been documented.2-5 All included patients with lupus nephritis, but while the series from Natal' gave a detailed list.

"Bound" globulin in the skin of patients with chronic discoid lupus erythematosus and systemic lupus erythematosus

NARCIS (Netherlands)

Cormane, R.H.

1964-01-01

In what respect chronic discoid lupus erythematosus is related to systemic lupus erythematosus is still uncertain. In discoid lupus the lupus-erythematosus (L.E.) phenomenon is negative, and the history does not suggest vascular lesions or involvement of serous membranes. In both diseases the

Avaliação da função e da lesão renal: um desafio laboratorial Evaluation of renal function and damage: a laboratorial challenge

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Fábio L. Sodré

2007-10-01

Full Text Available Atualmente a doença renal é um grande problema de saúde pública, que acomete milhares de pessoas no Brasil e no mundo. O estudo da função e dos diversos processos patológicos renais tem despertado o interesse de muitos pesquisadores, principalmente no campo do desenvolvimento de testes que auxiliem os médicos a estabelecer um diagnóstico precoce, classificar a doença de base, obter prognóstico seguro e monitorar terapêutica medicamentosa. Neste artigo sete marcadores de função e de lesão renal são avaliados: uréia, creatinina, cistatina C, proteinúria, dismorfismo eritrocitário, microalbuminúria e fração hepática das proteínas ligadas a ácidos graxos. É apresentado um breve histórico da utilização clínica e da fisiopatologia de cada um deles, seguidas de sua aplicabilidade e dos avanços técnicos e metodológicos disponíveis. Apesar de melhorias terem sido conseguidas e incorporadas à prática laboratorial, nenhum marcador atualmente disponível é completamente eficaz em analisar a função e/ou a lesão renal de forma precisa, sendo imprescindível o conhecimento de todos eles para uma correta avaliação desses testes comuns na rotina laboratorial.Nowadays, renal disease is an important public health problem, affecting millions of people in Brazil and in the world. The study of renal function and renal pathologic processes has aroused the interest of researchers, mainly in the field of development of new assays that could aid physicians in establishing early diagnosis, better classifying the disease, obtaining better outcome and monitoring drug therapeutics. In this article, seven laboratory markers of renal function or damage are evaluated: urea, creatinine, cystatin C, proteinuria, dysmorphic erythrocytes, microalbuminuria and liver-type fatty acid binding protein (L-FABP. For each one of them, a short historical report of its clinical utility and physiopathology is presented. Then technical and

Living with Lupus

Science.gov (United States)

... How Lupus Affects the Body Lupus and the Workplace Mental Health and Wellbeing Overlapping Diseases Reproductive Health Self-Advocacy Treatment Options all resource types Videos Articles Downloadable PDFs Slideshow Q & A List Personal Stories ...

Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models

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Marcin Klapczynski

2012-01-01

Full Text Available Introduction: Surgical 5/6 nephrectomy and adenine-induced kidney failure in rats are frequently used models of progressive renal failure. In both models, rats develop significant morphological changes in the kidneys and quantification of these changes can be used to measure the efficacy of prophylactic or therapeutic approaches. In this study, the Aperio Genie Pattern Recognition technology, along with the Positive Pixel Count, Nuclear and Rare Event algorithms were used to quantify histological changes in both rat renal failure models. Methods: Analysis was performed on digitized slides of whole kidney sagittal sections stained with either hematoxylin and eosin or immunohistochemistry with an anti-nestin antibody to identify glomeruli, regenerating tubular epithelium, and tubulointerstitial myofibroblasts. An anti-polymorphonuclear neutrophil (PMN antibody was also used to investigate neutrophil tissue infiltration. Results: Image analysis allowed for rapid and accurate quantification of relevant histopathologic changes such as increased cellularity and expansion of glomeruli, renal tubular dilatation, and degeneration, tissue inflammation, and mineral aggregation. The algorithms provided reliable and consistent results in both control and experimental groups and presented a quantifiable degree of damage associated with each model. Conclusion: These algorithms represent useful tools for the uniform and reproducible characterization of common histomorphologic features of renal injury in rats.

Sono-Guided Percutaneous Automated Gun Biopsy in Pediatric Renal Disease

International Nuclear Information System (INIS)

Kim, Jong Chul

1996-01-01

To evaluate whether sono-guided percutaneous automated gun biopsy is also useful in pediatricpatients with renal diseases. In the prone position of twenty pediatric patients with renal parenchymal diseases, percutaneous biopsy was done through lateral aspect of the lower pole of left kidney with automated biopsy gun under the guidance of ultrasonography. The biopsy needle was either of 18 or 20 gauge. The obtained core of renal tissue was examined with light, immunofluorescent or electron microscope by the renal pathologist. In 18 among 20 patients, adequate renal tissue core sufficient to be pathologically diagnosed was obtained. The histologic findings were as follows : IG A nephropathy (n = 2), lupus nephritis (n =2), minimal change glomerulonephritis (n = 5), membranoproliferative glomerulonephritis (n = 3), mesangialproliferative glomeru-lonephritis (n = 1), diffuse proliferative glomerulonephritis (n = 3), focalglomerulo-sclerosis (n = 1), membranous glomerulopathy (n = 1). No significant complications occurred during or after the biopsy. Sono-guided percutaneous renal biopsy using automated biopsy gun is also useful todiagnose renal parenchymal diseases without significant complications in pediatric patients

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

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Valeria Diaz-Rizo

Full Text Available There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN.In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN. A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02, whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07. Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001, but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02. Instead, leptin was not associated with LN.These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Lupus among Asians and Hispanics

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... this? Submit What's this? Submit Button Past Emails Lupus among Asians and Hispanics Recommend on Facebook Tweet ... compared with white women. Signs and Symptom of Lupus Lupus can affect people of all ages. However, ...

Diet and Nutrition With Lupus

Science.gov (United States)

... Facebook Pinterest Email Print Diet and nutrition with lupus Lupus Foundation of America April 19, 2018 Resource ... living Recipe collection Guidance on alcohol use with lupus Moderate use of alcohol is usually not a ...

Different expression patterns of renal Na+/K+-ATPase α-isoform-like proteins between tilapia and milkfish following salinity challenges.

Science.gov (United States)

Yang, Wen-Kai; Chung, Chang-Hung; Cheng, Hui Chen; Tang, Cheng-Hao; Lee, Tsung-Han

2016-12-01

Euryhaline teleosts can survive in a broad range of salinity via alteration of the molecular mechanisms in certain osmoregulatory organs, including in the gill and kidney. Among these mechanisms, Na + /K + -ATPase (NKA) plays a crucial role in triggering ion-transporting systems. The switch of NKA isoforms in euryhaline fish gills substantially contributes to salinity adaptation. However, there is little information about switches in the kidneys of euryhaline teleosts. Therefore, the responses of the renal NKA α-isoform protein switch to salinity challenge in euryhaline tilapia (Oreochromis mossambicus) and milkfish (Chanos chanos) with different salinity preferences were examined and compared in this study. Immunohistochemical staining in tilapia kidneys revealed the localization of NKA in renal tubules rather than in the glomeruli, similar to our previous findings in milkfish kidneys. Protein abundance in the renal NKA pan α-subunit-like, α1-, and α3-isoform-like proteins in seawater-acclimated tilapia was significantly higher than in the freshwater group, whereas the α2-isoform-like protein exhibited the opposite pattern of expression. In the milkfish, higher protein abundance in the renal NKA pan α-subunit-like and α1-isoform-like proteins was found in freshwater-acclimated fish, whereas no difference was found in the protein abundance of α2- and α3-isoform-like proteins between groups. These findings suggested that switches for renal NKA α-isoforms, especially the α1-isoform, were involved in renal osmoregulatory mechanisms of euryhaline teleosts. Moreover, differences in regulatory responses of the renal NKA α-subunit to salinity acclimation between tilapia and milkfish revealed that divergent mechanisms for maintaining osmotic balance might be employed by euryhaline teleosts with different salinity preferences. Copyright © 2016 Elsevier Inc. All rights reserved.

Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

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Qing-Rong Pan

2014-07-01

Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

Living with Lupus (For Parents)

Science.gov (United States)

... Videos for Educators Search English Español Living With Lupus KidsHealth / For Parents / Living With Lupus What's in ... disease for both doctors and their patients. About Lupus A healthy immune system produces proteins called antibodies ...

Acute renal failure after rifampicin

Directory of Open Access Journals (Sweden)

Adriana Weinberg

1984-12-01

Full Text Available A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP, isoniazid (INH and ethambutol (EMB. This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

Incidence of systemic lupus erythematosus and lupus nephritis in Denmark

DEFF Research Database (Denmark)

Hermansen, Marie-Louise From; Lindhardsen, Jesper; Torp-Pedersen, Christian

2016-01-01

Objective. To determine the incidence of systemic lupus erythematosus (SLE) and SLE with concomitant or subsequent lupus nephritis (LN) in Denmark during 1995.2011, using data from the Danish National Patient Registry (NPR).  Methods. To assess the incidence of SLE, we identified all persons aged...

Radical improvement of signs and symptoms in systemic lupus erythematosus when treated with hemodiafiltration with endogenous reinfusion dialysis.

Science.gov (United States)

Solano, Francesco Giuseppe; Bellei, Elisa; Cuoghi, Aurora; Caiazzo, Marialuisa; Bruni, Francesco

2015-01-01

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). In the kidney, immune complexes and autoantibodies activate mesangial cells that secrete cytokines that can further amplify inflammatory processes. We present the case of a 42-year-old woman with lupus nephritis accompanied by periods of exacerbation of SLE, with necrotic-like skin lesions, psoriatic arthritis without skin psoriasis, purpura of the lower limb, petechial rash, joint pain, fever, eyelid edema with bilateral conjunctival hyperemia and itching. The patient underwent a dialytic treatment of hemodiafiltration with endogenous reinfusion. The technique uses the super-high-flux membrane Synclear 02 (SUPRA treatment) coupled with an adsorbent cartridge that has affinity for many toxins and mediators. Fever and joint pain were immediately reduced after treatment and, subsequently, there was a notable reduction of the skin damage. Prednisone and immunosuppressive drugs were gradually reduced until complete suspension. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer was performed for identification of proteins captured by a resin bed during a dialysis session of the patient. This technique identified several biomarkers of kidney injuries, uremic toxins, fragments of immunoglobulins, antigens involved in antiphospholipid syndrome and a new marker (α-defensin) that correlated significantly with disease activity. The removal of these different proteins could possibly provide an explanation of the improvement in the patient's symptoms and the normalization of her SLE. SUPRA coupled with an adsorption may be a promising new technique for the treatment of lupus nephritis.

A Case of Systemic Lupus Erythematosus Confused with Infective Endocarditis

OpenAIRE

Sibel Serin; Kevser Kutlu Tatar; Tayyibe Saler

2014-01-01

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease resulting from immune system-mediated tissue damage. Clinical findings of SLE can involve skin, kidney, central nervous system, cardiovascular system, serosal membranes, and the hematologic and immune systems. In the differential diagnosis, other connective tissue diseases, infective endocarditis, infections such as viral hepatitis, endocrine disorders such as hypothyroidism, sarcoidosis, and some malignant tumors should...

A 3-year follow-up of a patient with acute renal failure caused by thrombotic microangiopathy related to antiphospholipid syndrome: case report.

Science.gov (United States)

Zhou, X-J; Chen, M; Wang, S-X; Zhou, F-D; Zhao, M-H

2017-06-01

Background Microvascular manifestations of antiphospholipid antibody syndrome in the kidneys include acute renal failure, thrombotic microangiopathy and hypertension. Therapy has been largely empiric. Case report A 49-year-old Chinese man presented with anuric acute renal failure without abundant proteinuria and heavy haematuria, but markedly low levels of urinary sodium, potassium and chlorine upon admission. On day 1 of hospitalization, his thrombocytopenia, anaemia and renal failure showed rapid progression. The presence of lupus anticoagulant and vascular ischaemia of the small vessels in renal arteriography were also observed. Anticoagulants, continuous renal replacement therapy, glucocorticoids and six sessions of plasma exchange were started. After the fourth plasma exchange (on day 20), his urine output increased and began to normalize. On day 25, haemodialysis was stopped and his general condition gradually improved. A renal biopsy was subsequently performed, and the histopathological diagnosis was thrombotic microangiopathy due to antiphospholipid antibody syndrome. A further 3-year follow-up showed that his haemoglobin level, platelet count and serum creatinine were within the normal range, with stable blood pressure. Conclusion Treatment modalities such as anticoagulation, immunosuppression and plasma exchange are likely to be necessary when severe acute renal failure combined with thrombotic microangiopathy present in nephropathy of antiphospholipid antibody syndrome.

Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

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Mariana Postal

2012-01-01

Full Text Available OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI. Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50, 64 firstdegree relatives (mean age 39.95±5.66, and 57 healthy (mean age 19.30±4.97 controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their firstdegree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in

The impact of the EUSCLE Core Set Questionnaire for the assessment of cutaneous lupus erythematosus.

Science.gov (United States)

Kuhn, A; Patsinakidis, N; Bonsmann, G

2010-08-01

Epidemiological data and standard European guidelines for the diagnosis and treatment of cutaneous lupus erythematosus (CLE) are lacking in the current literature. In order to provide a standardized tool for an extensive consistent data collection, a study group of the European Society of Cutaneous Lupus Erythematosus (EUSCLE) recently developed a Core Set Questionnaire for the assessment of patients with different subtypes of CLE. The EUSCLE Core Set Questionnaire includes six sections on patient data, diagnosis, skin involvement, activity and damage of disease, laboratory analysis, and treatment. An instrument like the EUSCLE Core Set Questionnaire is essential to gain a broad and comparable data collection of patients with CLE from different European centres and to achieve consensus concerning clinical standards for the disease. The data will also be important for further characterization of the different CLE subtypes and the evaluation of therapeutic strategies; moreover, the EUSCLE Core Set Questionnaire might also be useful for the comparison of data in clinical trials. In this review, the impact of the EUSCLE Core Set Questionnaire is discussed in detail with regard to clinical and serological features as well as therapeutic modalities in CLE.

Phospholipid Syndrome and Vasculitis as a presentation of Systemic Lupus Erythematosus. Case report.

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Sila Castellón Mortera

2013-09-01

Full Text Available The systemic Lupus Erythematosus is presented, generally, as a poli articular syndrome, with a long period of fever nephritico or nephrotico; other clinical ways are: neuropsychiatry, vasculitis, etc. They appeared in a progressive manner; but in rare cases as a sickness debutant. It has not being reported in Sancti Spiritus Province patients in which matches the debut of the systemic Lupus Erythematosus with the manifestations of phospholipid syndrome. A Woman with 24 years of age is hospitalized having vasculitis, articular pains, thrombose in her right foot, detecting anticoagulante lupico and possitive Rematoideo factor with periferic pattern diffused in the Inmunoelectroforesis. 5 years later was hospitalized again with poliserositis. She had a positive evolution with a dose in a month of Intacglobin and anticoagulante treatment. Two years later she was hospitalized with articular pains proving she had livedo reticular on her left knee and Raynaud phenomenon on her foot. Beta Prebeta Index and high triglycerides. Lupico anticoagulant positive again. A treatment with Intacglobin and Prednisona was given to the patient with a better clinic without being hospitalized again. There is no evidence (at 17 years of age of a sickness debut of renal dissorder. It is about a Systemic Lupus Eritematoso which debut was a vasculitis and a Phospholipid Syndrome associated.

Computerized tomography data on CNS affection in systemic lupus erythematosus. Porazhenie tsentral'noj nervnoj sistemy pri sistemnoj krasnoj volchanke po dannym komp'yuternoj tomografii

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Ivanova, M M; Bliznyuk, O I; Todua, F I; Tumanova, A A

1989-01-01

Computed tomography (CT) of the brain was employed in 40 patients with systemic lupus erythematosus (SLE). Clinical cerebral pathology was obvious in 30 and absent in 10 patients. By CT cerebral symptoms were divided of 4 groups. Clinical symptom complexes of CNS defects and SLE were reflected on definite CT images correlated with focal damage to the brain. CT picture of enlarged subarachnoid space, ventricles and basal cisterns can be observed in SLE patients without neurological symptoms. This indicated likely subclinical cerebral affection.

Graviditetskomplikationer hos en patient med systemisk lupus erythematosus og lupus nefritis

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Bisgaard, Helene; Jacobsen, Søren; Tvede, Niels

2014-01-01

A woman with systemic lupus erythematosus (SLE) and lupus nephritis had two pregnancies which both resulted in complications known to be associated with SLE, i.e. late abortion, preterm delivery and pre-eclampsia. We conclude that disease quiescence is important for a successful outcome...

Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients.

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Calvo-Alén, J; Alarcón, G S; Campbell, R; Fernández, M; Reveille, J D; Cooper, G S

2005-09-01

To determine to what extent the diagnosis of systemic lupus erythematosus (SLE) in deceased lupus patients is under-reported in death certificates, and the patient characteristics associated with such an occurrence. The death certificates of 76 of the 81 deceased SLE patients from two US lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for Carolina Lupus Study), including 570 and 265 patients, respectively, were obtained from the Offices of Vital Statistics of the states where the patients died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas). Both cohorts included patients with SLE as per the American College of Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of < or =5 yr. The median duration of follow-up in each cohort at the time of these analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were performed comparing patients with SLE recorded anywhere in the death certificate and those without it. A multivariable logistic regression model was performed to identify the variables independently associated with not recording SLE in death certificates. In 30 (40%) death certificates, SLE was not recorded anywhere in the death certificate. In univariable analyses, older age was associated with lack of recording of SLE in death certificates [mean age (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom SLE was omitted and included on the death certificates, respectively, P = 0.005]. Patients without health insurance, those dying of a cardiovascular event and those of Caucasian ethnicity were also more likely to be in the non-recorded group. In the multivariable analysis, variables independently associated with not recording SLE as cause of death were older age [odds ratio = (95% confidence interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health insurance [4.649 (1.152-18.768); P = 0.031]. A high proportion of SLE diagnoses are not

An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice

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Nelson, Richard K.; Gould, Karen A.

2015-01-01

Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB×NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4+ and CD8+ T cells, the proportion of activated CD4+ T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cells apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. PMID:26385218

Scleroderma renal crisis in a case of mixed connective tissue disease

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Mukul Vij

2014-01-01

Full Text Available Mixed connective tissue disease (MCTD is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma and polymyositis. Scleroderma renal crisis (SRC is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

Scleroderma renal crisis in a case of mixed connective tissue disease.

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Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

Benfotiamine Protects against Peritoneal and Kidney Damage in Peritoneal Dialysis

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Kihm, Lars P.; Müller-Krebs, Sandra; Klein, Julia; Ehrlich, Gregory; Mertes, Laura; Gross, Marie-Luise; Adaikalakoteswari, Antonysunil; Thornalley, Paul J.; Hammes, Hans-Peter; Nawroth, Peter P.; Zeier, Martin; Schwenger, Vedat

2011-01-01

Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peri...

Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

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Durcan, Laura; Petri, Michelle

2016-01-01

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.

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Hristova, M H; Stoyanova, V S

2017-12-01

Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Genetic defects in the complement as well as functional deficiency due to antibodies against its components lead to different pathological conditions, usually clinically presented. Among them hypocomplementemic urticarial vasculitis, different types of glomerulonephritis as dense deposit disease, IgA nephropathy, atypical haemolytic uremic syndrome and lupus nephritis are very common. These antibodies cause conformational changes leading to pathological activation or inhibition of complement with organ damage and/or limited capacity of the immune system to clear immune complexes and apoptotic debris. Finally, we summarize the role of complement antibodies in the pathogenesis of systemic lupus erythematosus and discuss the mechanism of some related clinical conditions such as infections, thyroiditis, thrombosis, acquired von Willebrand disease, etc.

Outcome of lupus nephritis in childhood onset SLE in North and Central India: single-centre experience over 25 years.

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Srivastava, P; Abujam, B; Misra, R; Lawrence, A; Agarwal, V; Aggarwal, A

2016-04-01

Childhood SLE (cSLE) has a higher prevalence of lupus nephritis (LN), and there are ethnic variations in response to treatment as well as outcome of LN. There are limited data on long-term outcome of LN in cSLE from the Indian subcontinent. Retrospective analysis of case records of patients with cSLE (satisfying revised American College of Rheumatology (ACR) 1997 criteria for diagnosis) and age of onset Collaborating Clinics (SLICC)/ACR damage score was 0.79 ± 1.13. Actuarial ESRD-free survival at five, 10 and 15 years was 91.1%, 79% and 76.2%, and five-, 10- and 15-year renal survival was 93.8%, 87.1% and 84%, respectively. Although multiple factors individually predicted poor outcome (death/ESRD), only raised serum creatinine at onset (R square = 0.65, p ≤ 0.0001) and damage accrual (R square = 0.62, p ≤ 0.0001) remained significant on multivariate analysis. Eleven (8.2%) children died during the follow-up period, and infections were the leading cause of mortality. Long-term outcome of LN in cSLE in our cohort was better than previous reports from India. However, a high rate of major infection still remains the leading cause of mortality. © The Author(s) 2015.

Antiphospholipid syndrome (APS) nephropathy in catastrophic, primary, and systemic lupus erythematosus-related APS.

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Tektonidou, Maria G; Sotsiou, Flora; Moutsopoulos, Haralampos M

2008-10-01

Renal involvement in antiphospholipid syndrome (APS) has been poorly recognized. A renal small-vessel vasculopathy, defined as APS nephropathy, has recently been observed in small series of patients with primary APS (PAPS) and systemic lupus erythematosus (SLE)-APS. We examined the renal histologic, clinical, and laboratory characteristics of different groups of patients with APS including catastrophic APS (CAPS). Our study included all CAPS (n=6), PAPS (n=8), and SLE-APS (n=23) patients with biopsy-proven renal involvement who were referred to our departments. The kidney biopsy specimens were retrospectively examined by the same renal pathologist. APS nephropathy was diagnosed as previously described. Demographic, clinical, and laboratory data were recorded. All patients with CAPS had acute and chronic renal vascular lesions compatible with diagnosis of APS nephropathy. Thrombotic microangiopathy (TMA), the acute lesion, was observed in all CAPS patients. Fibrous intimal hyperplasia of interlobular arteries (FIH) and focal cortical atrophy (FCA) were the most common chronic vascular lesions, occurring in 4 of 6 (66.7%) and 3 of 6 (50%) patients with CAPS, respectively. TMA was detected in 3 of 8 (37.5%) patients with PAPS and in 8 of 23 (35%) patients with SLE-APS, while FIH and FCA were found with similar frequencies in all 3 groups. Hypertension, proteinuria, hematuria, and renal insufficiency were the most common renal manifestations of all APS groups. Acute and chronic APS nephropathy lesions were detected in all 3 APS groups. Acute lesions were more prominent in CAPS, while chronic lesions were found with similar frequencies in all groups. Hypertension, proteinuria, hematuria, and renal insufficiency were the most common renal manifestations of all APS groups.

Oral manifestations of lupus.

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Menzies, S; O'Shea, F; Galvin, S; Wynne, B

2018-02-01

Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

Subacute cutaneous lupus erythematosus presenting as poikiloderma.

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Hughes, R

2012-02-01

Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus erythematosus (LE), which accounts for 10-15% of all cases of cutaneous LE, occurring most commonly in young to middle-aged white women. Diagnosis is based on the detection of anti-Ro\\/SS-A antibodies in the skin and serum, characteristic clinical and histological cutaneous involvement, and relatively mild systemic involvement. Several unusual variants of SCLE have been reported including erythrodermic SCLE, SCLE with vitiligo-like lesions, acral SCLE and bullous SCLE. Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are currently only two case reports, comprising five individual cases, in the literature. We present a case of SCLE in which the main clinical findings were an extensive photodistributed poikilodermatous rash and alopecia.

Renal tubular dysfunction presenting as recurrent hypokalemic periodic quadriparesis in systemic lupus erythematosus

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D Prasad

2014-01-01

Full Text Available We report recurrent hypokalemic periodic quadriparesis in a 30-year-old woman. Patient had also symptoms of multiple large and small joint pain, recurrent oral ulceration, photosensitivity and hair loss that were persisting since last 6 months and investigations revealed systemic lupus erythematosus (SLE with distal tubular acidosis. Our patient was successfully treated with oral potassium chloride, sodium bicarbonate, hydroxychloroquine and a short course of steroids. Thus, tubular dysfunction should be carefully assessed in patients with SLE.

BERTAHAN DENGAN LUPUS: GAMBARAN RESILIENSI PADA ODAPUS

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Anggun Resdasari Prasetyo

2015-01-01

Full Text Available Abstract Lupus is a chronic, autoimmune disease in which an abnormal immune system can cause inflammation on several organ or body systems. The risk of mortality rate caused by Lupus is high and late diagnosis is also prevalent which impact the psychological aspect of individual affected with Lupus (so-called Odapus. Therefore, resiliency is needed; that is individual ability to survive and keep optimistic attitude towards recovery. This study aims to describe the resiliency of the affected individuals with Lupus. This is a qualitative study. Eight persons affected with Lupus who were still coping with Lupus participated in this study. The results indicated that subjects developed a negatives constructs to adapt with Lupus. Therefore, psychological intervention is needed to improve their resiliency.

B cell signature during inactive systemic lupus is heterogeneous: toward a biological dissection of lupus.

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Jean-Claude Garaud

Full Text Available Systemic lupus erythematosous (SLE is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomas of quiescent lupus patients to normal B cell transcriptomas. When the statistical analysis is performed on the entire group of patients, the differences between patients and controls appear quite weak with only 14 mRNA genes having a false discovery rate ranging between 11 and 17%, with 6 underexpressed genes (PMEPA1, TLR10, TRAF3IP2, LDOC1L, CD1C and EGR1. However, unforced hierarchical clustering of the microarrays reveals a subgroup of lupus patients distinct from both the controls and the other lupus patients. This subgroup has no detectable clinical or immunological phenotypic peculiarity compared to the other patients, but is characterized by 1/an IL-4 signature and 2/the abnormal expression of a large set of genes with an extremely low false discovery rate, mainly pointing to the biological function of the endoplasmic reticulum, and more precisely to genes implicated in the Unfolded Protein Response, suggesting that B cells entered an incomplete BLIMP1 dependent plasmacytic differentiation which was undetectable by immunophenotyping. Thus, this microarray analysis of B cells during quiescent lupus suggests that, despite a similar lupus phenotype, different biological roads can lead to human lupus.

Genetics Home Reference: systemic lupus erythematosus

Science.gov (United States)

... Twitter Home Health Conditions Systemic lupus erythematosus Systemic lupus erythematosus Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation ...

Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

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Imed Helal

2011-01-01

Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

Ectopic Axillary Breast during Systemic Lupus

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Besma Ben Dhaou

2012-01-01

Full Text Available Many breast changes may occur in systemic lupus erythematosus. We report a 41-year-old woman with lupus who presented three years after the onset of lupus an ectopic mammary gland confirmed by histological study.

Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

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Martin H de Borst

Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

THE IMPORTANCE OF 99m-Tc DMSA RENAL SCINTIGRAPHY IN EVALUATION OF RENAL LESIONS IN CHILDREN WITH ACUTE PYELONEPHRITIS

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N Ataei

2008-11-01

Full Text Available "nUrinary tract infection (UTI may lead to irreversible changes in renal parenchyma. Early diagnosis using scintigraphy with technetium-99m-labeled dimercaptosuccinic acid (DMSA scan and early treatment may decrease or prevent development of renal parenchymal lesions. The aim of this study was to assess the occurrence of renal parenchymal lesion in children admitted with a first-time symptomatic UTI and to evaluate the relation between renal parenchymal damage and severity of vesicoureteral reflux (VUR. A total of 102 children with first time acute pyelonephritis (APN were enrolled in the study. All children studied with DMSA scan and ultrasonography (US. Voiding cystourethrography (VCUG was performed in 98 children when urine culture became negative. Changes on the DMSA scan and US were found in 178 (88% and 5 (2.4% out of 203 renal units during the acute phase, respectively. All abnormal renal units on US showed severe parenchymal involvement on DMSA. We also found significant correlation between severity of VUR and abnormal US results on kidneys. Of 40 kidneys with reflux, 38 (95% were found to have abnormal renal scan. Among 155 kidneys with non-refluxing ureters 132 (85.2% revealed parenchymal changes on renal cortical scintigraphy. Kidneys with moderate to severe reflux were more likely to have severe renal involvement. We found a high incidence of renal parenchymal changes in children with APN. Additionally, renal involvement was significantly higher in children with moderate to severe reflux. When there are high-grade VUR and female gender, the risk of renal parenchymal involvement is higher.

Haematological manifestations of lupus

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Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

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Jianmin Ran

2014-01-01

Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

Pregnancy complications in a patient with systemic lupus erythematosus and lupus nephritis

DEFF Research Database (Denmark)

Bisgaard, Helene; Jacobsen, Søren; Tvede, Niels

2014-01-01

A woman with systemic lupus erythematosus (SLE) and lupus nephritis had two pregnancies which both resulted in complications known to be associated with SLE, i.e. late abortion, preterm delivery and pre-eclampsia. We conclude that disease quiescence is important for a successful outcome...

Polymorphisms within Toll-like receptors are associated with systemic lupus erythematosus in a cohort of Danish females

DEFF Research Database (Denmark)

Laska, Magdalena Janina; Troldborg, Anne; Hansen, Bettina

2014-01-01

and to determine the expression of various TLRs in peripheral blood mononuclear cells (PBMCs) of patients with SLE. METHODS: The TLR polymorphisms in a cohort of 143 Danish lupus patients and 432 healthy Danish blood donors were analysed. Groups were age matched. Genotyping for the TLR single......: These results obtained from a female lupus population of Danish ancestry suggest that variations in TLR3, TLR8 and TLR9 genes are implicated in the pathogenesis of the disease. If these polymorphisms are associated with innate immune dysfunction they may add to the growing field of theoretically well founded...

Quality-of-life measurements in multiethnic patients with systemic lupus erythematosus: cross-cultural issues.

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Toloza, Sergio M A; Jolly, Meenakshi; Alarcón, Graciela S

2010-08-01

Although the survival rate for systemic lupus erythematosus (SLE) has improved dramatically during the past 50 years, the quality of life of patients afflicted with this disease remains poor. Currently existent measures of disease activity and damage in SLE do not capture the patient's perspective and health-related quality of life (HRQoL). Most studies in SLE pertaining to HRQoL are from developed Western societies, with only a few from others. These studies have been conducted predominantly in women and using the Medical Outcomes Survey Short Form 36, a generic HRQoL instrument that has been shown not to be sensitive to change in lupus. Existent lupus-specific HRQoL measures have not yet been used in SLE clinical trials. New HRQoL research tools are currently undergoing validation in different countries, languages, and cultural settings, which may help dissect the underlying role of socioeconomic status and specific disease-related features that impact SLE-related quality of life.

Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine

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John P. O’Laughlin

2016-01-01

Full Text Available We present a case of a syncopal episode resulting from significant QT interval prolongation in a patient on hydroxychloroquine for the treatment of systemic lupus erythematosus and end stage renal disease. The patient had been treated with hydroxychloroquine for two years prior to presentation. After thorough workup for secondary causes of QT interval prolongation hydroxychloroquine was discontinued and the patient’s QT interval shortened. The patient was treated with mexiletine to prevent sudden ventricular arrhythmias, which was unique compared to other documented cases in which lidocaine was used. The patient was noted to have mild prolongation of the QT interval on electrocardiogram prior to initiation of hydroxychloroquine therapy which was exacerbated by its use and may have been caused due to toxicity from underlying renal failure.

Percutaneous ultrasound-guided renal biopsy: A Libyan experience

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Mishra, A.; Tarsin, R.; ElHabbash, B.; Zagan, N.; Markus, R.; Drebeka, S.; AbdElmola, K.; Shawish, T.; Shebani, A.; AbdElmola, T.; ElUsta, A.; Ehtuish, E. F.

2010-01-01

This study was done to assess the safety and efficacy of ultrasound-guided percutaneous renal biopsy (PRB), to ascertain the risk factors for complications and determine the optimal period of observation. The radiologist (A.M.) at the National Organ Transplant Centre, Central Hospital, Tripoli, Libya, performed 86 PRBs between February 1, 2006, and January 31, 2008, using an automated biopsy gun with 16-gauge needle. Coagulation profile was done in all the patients. All patients were kept on strict bed rest for six hours post-procedure. Eighty six renal biopsies were performed on 78 patients referred from rheumatology department and eight post-kidney transplant recipients; 23 were males with age range 15 – 56 years and 63 females with age range 16 – 66 years. A mean of 17.5 glomeruli were present in each specimen. A glomerular yield of less than five glomeruli was seen in four biopsies. Class I lupus nephritis (LN) was seen in 1 patient, class II lupus nephritis in 7 patients, class III LN in 13 patients and class IV LN in 29 patients. All the eight renal allografts were diagnosed as acute tubular necrosis or acute interstitial rejection. The risk of post-biopsy bleeding was higher in women, older patients and higher PTT. The overall complication rate was 5.8%. Three complications were observed within six hours of biopsy. No late complication was seen. PRB under real-time ultrasound-guidance is a safe and efficacious procedure to establish the histological diagnosis and should be done as out-patient procedure. Observation time of six hours post-biopsy is optimal. PMID:20835320

Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus

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Rodgers, D T; Pineda, M A; Suckling, C J; Harnett, W

2015-01-01

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. PMID:26085597

Alteraciones renales en la drepanocitosis Renal disorders in sickle cell disease

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Aramís Núñez-Quintana

2011-06-01

Full Text Available La drepanocitosis está asociada con un amplio espectro de alteraciones renales que tienen su base en la falciformación de los eritrocitos en los vasos de la médula renal, que conduce a fenómenos de isquemia, microinfartos y anomalías de la función tubular. Se producen también alteraciones glomerulares funcionales reversibles de la autorregulación renal (hiperfiltración, que pueden conducir a cambios anatómicos irreversibles con glomeruloesclerosis segmentaria focal. Estas anomalías se expresan tempranamente como microalbuminuria, proteinuria y de forma mas tardía, como síndrome nefrótico e insuficiencia renal crónica. Medidas terapéuticas como el uso de inhibidores de la enzima convertidora de la angiotensina II, de los bloqueadores del receptor de la angiotensina II, asociados o no con la hidroxiurea, pueden prevenir o retardar el daño glomerular. En el presente trabajo se exponen de forma resumida aspectos relacionados con la fisiopatología del daño renal en la drepanocitosis y su tratamiento.Sickle cell disease is associated with a wide range of renal disorders resulting from the falciformation of erythrocytes in vessels of the renal medulla, leading to ischemia, microinfarctions and tubular function abnormalities. Reversible glomerular functional renal self-regulation disorders (hyperfiltration also occur, which may lead to irreversible anatomical changes with focal segmental glomerular sclerosis. These anomalies are expressed at an early stage as microalbuminuria and proteinuria, and at a later stage as nephrotic syndrome and chronic renal failure. Therapeutic measures such as the use of angiotensin-II converting enzyme inhibitors and angiotensin-II receptor blockers, associated or not with hydroxyurea, may either prevent or delay glomerular damage. The paper succinctly presents the physiopathology of renal damage in drepanocytosis and its treatment.

Outcome of pregnancy in patients with inactive systemic lupus erythromatosus and minimal proteinuria

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Alshohaib Saad

2009-01-01

Full Text Available Systemic lupus erythematosus (SLE is a multisystem disease. This study was under-taken to assess the outcome of pregnancies in patients with inactive SLE. We prospectively studied 20 female patients with diagnosis of stable class IV Lupus nephritis followed up at King Abdul Aziz University Hospital, in Jeddah, Saudi Arabia between 1998 and 2008. Before each pregnancy all the patients had their blood pressure, serum creatinine, creatinine clearance, serology for SLE and 24-hour urine protein excretion measured and then repeated at monthly intervals during the pregnancy. Statistical analysis was performed using the Wilcoxon signed-rank test. Despite having negative antinuclear antibody (ANA significant complications were observed during pregnancy. The daily proteinuria during 34-36 weeks′ gestation was significantly higher (P< 0.05 than during 32 weeks. Two patients had abortions one stillbirth and 2 required termination of the pregnancy; one due to severe hypertension, and other due to renal impairment. One patient developed HELLP (hemolysis, elevated liver enzymes, low platelets syndrome. 14 patients had a successful preg-nancy, including 4 requiring a cesarian section. In conclusion, although no clinical evidence of lupus disease activity was demonstrated pre-conception proteinuria significantly increased during pregnancy along with maternal and fetal complications. Pregnant females with diagnosis of SLE need a multidisciplinary care during the pregnancy and post-partum period.

Methyl salicylate 2-O-β-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction.

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He, Yang-Yang; Yan, Yu; Zhang, Hui-Fang; Lin, Yi-Huang; Chen, Yu-Cai; Yan, Yi; Wu, Ping; Fang, Jian-Song; Yang, Shu-Hui; Du, Guan-Hua

2016-01-01

Systemic lupus erythematosus (SLE), with a high incidence rate and insufficient therapy worldwide, is a complex disease involving multiple organs characterized primarily by inflammation due to deposition of immunocomplexes formed by production of autoantibodies. The mechanism of SLE remains unclear, and the disease still cannot be cured. We used pristane to induce SLE in female BALB/c mice. Methyl salicylate 2- O -β-d-lactoside (MSL; 200, 400, and 800 mg/kg) was orally administered 45 days after pristane injection for 4.5 months. The results showed that MSL antagonized the increasing levels of multiple types of antibodies and cytokines in lupus mice. MSL was found to suppress joint swelling and have potent inhibitory effect on arthritis-like symptoms. MSL also significantly decreased the spleen index and expression of inflammatory markers in the lupus mice. MSL protected the kidneys of lupus mice from injury through inhibiting the expression of inflammatory cytokines and reducing the IgG and C3 immunocomplex deposits. Further Western blot assays revealed that the downregulation of the intracellular inflammatory signals of NFκB and JAK/STAT3 might be the potential molecular mechanisms of the pharmacological activity of MSL against SLE in vivo. These findings may demonstrate that MSL has the potential to be a useful and highly effective treatment for SLE.

The effect of hydroxychloroquine on lupus erythematosus-like skin lesions in MRL/lpr mice.

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Shimomatsu, Tatsuya; Kanazawa, Nobuo; Mikita, Naoya; Nakatani, Yumi; Li, Hong-Jin; Inaba, Yutaka; Ikeda, Takaharu; Kondo, Toshikazu; Furukawa, Fukumi

2016-09-01

To evaluate the effect and safety of hydroxychloroquine (HCQ) on lupus erythematosus (LE)-like skin lesions in the MRL/lpr mouse, a model for systemic LE (SLE). We divided the MRL/lpr mice into three groups that were given: (1) drinking water, (2) HCQ at a dose of 4 mg/kg/d, or (3) HCQ at a dose of 40 mg/kg/d. The HCQ was administered to examine the effect and safety of HCQ on skin lesions and the number of infiltrating cells including mast cells in the dermis. Six of 13 mice in the group given drinking water, 3 of 11 mice in the group administered low-dose HCQ (4 mg/kg/d), and 1 of 10 mice in the group administered high-dose HCQ (40 mg/kg/d) presented the skin lesions. The average number of mast cells was 81, 50, and 12 (magnification, ×100), the mortality rate was 24%, 8%, and 9% and the mean body weight gain was 4.6 g, 8.0 g and 5.1 g, respectively. HCQ was demonstrated to decrease the appearance of LE-like lesions and the number of mast cells in the dermis. Furthermore, there were no obvious systemic adverse effects. This study provides evidence that suggests benefits in human patients.

Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury.

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Pressly, Jeffrey D; Mustafa, Suni M; Adibi, Ammaar H; Alghamdi, Sahar; Pandey, Pankaj; Roy, Kuldeep K; Doerksen, Robert J; Moore, Bob M; Park, Frank

2018-02-01

Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with elevated rates of mortality. Therapies to treat AKI are currently not available, so identification of new targets that can be modulated to ameliorate renal damage upon diagnosis of AKI is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295 [3'-methyl-4-(2-(thiophen-2-yl)propan-2-yl)biphenyl-2,6-diol], was designed, synthesized, and tested in vitro and in silico. Molecular docking of SMM-295 into a CB2 active-state homology model showed that SMM-295 interacts well with key amino acids to stabilize the active state. In human embryonic kidney 293 cells, SMM-295 was capable of reducing cAMP production with 66-fold selectivity for CB2 versus cannabinoid receptor 1 and dose-dependently increased mitogen-activated protein kinase and Akt phosphorylation. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI, where SMM-295 was immediately administered upon reperfusion of the kidneys after the ischemia episode. Histologic damage assessment 48 hours after reperfusion demonstrated reduced tubular damage in the presence of SMM-295. This was consistent with reduced plasma markers of renal dysfunction (i.e., creatinine and neutrophil gelatinase-associated lipocalin) in SMM-295-treated mice. Mechanistically, kidneys treated with SMM-295 were shown to have elevated activation of Akt with reduced terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL)-positive cells compared with vehicle-treated kidneys after IRI. These data suggest that selective CB2 receptor activation could be a potential therapeutic target in the treatment of AKI. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Childhood-onset bullous systemic lupus erythematosus.

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Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A

2014-11-01

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Experimental anti-GBM nephritis as an analytical tool for studying spontaneous lupus nephritis.

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Du, Yong; Fu, Yuyang; Mohan, Chandra

2008-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that results in immune-mediated damage to multiple organs. Among these, kidney involvement is the most common and fatal. Spontaneous lupus nephritis (SLN) in mouse models has provided valuable insights into the underlying mechanisms of human lupus nephritis. However, SLN in mouse models takes 6-12 months to manifest; hence there is clearly the need for a mouse model that can be used to unveil the pathogenic processes that lead to immune nephritis over a shorter time frame. In this article more than 25 different molecules are reviewed that have been studied both in the anti-glomerular basement membrane (anti-GBM) model and in SLN and it was found that these molecules influence both diseases in a parallel fashion, suggesting that the two disease settings share common molecular mechanisms. Based on these observations, the authors believe the experimental anti-GBM disease model might be one of the best tools currently available for uncovering the downstream molecular mechanisms leading to SLN.

Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus

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Nossent, J.; Kiss, Adrian Emil; Rozman, B.

2010-01-01

An inception cohort of patients with systemic lupus erythematosus from 14 European centres was followed for up to 5 years in order to describe the current early disease course. At inclusion patients (n = 200, 89% female, mean age 35 years, 97% Caucasian, mean SLEDAI 12.2) fulfilled a mean of 6......% respectively. During the mean follow-up of 4.1 years 25% entered a state of early disease quiescence by global physician assessment, but the overall risk of subsequent flare was 60%. Maximum SLEDAI scores decreased over time, but 45% of patients accrued damage (SDI >= 1) for which baseline presence...... of proteinuria and persistent disease activity were independent predictors. The results indicate minor differences in SLE presentation and treatment within various regions of Europe and a high diagnostic reliance on anti-dsDNA Ab. Despite early reductions in disease activity and improved mortality, the risk...

Induction of a systemic lupus erythematosus-like disease in mice by a common human anti-DNA idiotype

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Mendlovic, S.; Brocke, S.; Meshorer, A.; Mozes, E.; Shoenfeld, Y.; Bakimer, R.; Ben-Bassat, M.

1988-01-01

Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. The authors report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE

Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

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Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

Epidemiology of cutaneous lupus erythematosus and the associated risk of systemic lupus erythematosus

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Petersen, M Prütz; Möller, S; Bygum, A

2018-01-01

Objectives The objectives of this paper are to describe the epidemiology of cutaneous lupus erythematosus (CLE) and its subtypes in Denmark, and to investigate the probability of receiving a subsequent diagnosis of systemic lupus erythematosus (SLE) and the related time course. Methods A nationwide...

Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

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Paolo Durigutto

2017-09-01

Full Text Available Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI. As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice.

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Nelson, R K; Gould, K A

2016-02-01

Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell-specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB × NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4(+) and CD8(+) T cells, the proportion of activated CD4(+) T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cell apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. © The Author(s) 2015.

Increased risk of depression in patients with cutaneous lupus erythematosus and systemic lupus erythematosus

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Hesselvig, J H; Egeberg, A; Kofoed, K

2018-01-01

BACKGROUND: Reported prevalences of depression in patients with systemic lupus erythematosus (SLE) range widely, while the prevalence of depression in cutaneous lupus erythematosus (CLE) remains severely understudied. OBJECTIVES: To examine whether patients with SLE or CLE have increased risk...... of primary and secondary care, analyses of risk for depression and antidepressant use were performed in Cox regression models adjusted for age, sex, socio-economic status, smoking, alcohol abuse, prior depression, and prior antidepressant use. RESULTS: A total of 3,489 patients with lupus erythematosus were...

Unmasking of complements using proteinase-K in formalin fixed paraffin embedded renal biopsies

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R Nada

2016-01-01

Full Text Available Renal biopsy interpretation requires histopathology, direct immunofluorescence (DIF and electron microscopy. Formalin-fixed, paraffin-embedded tissue (FFPE sent for light microscopy can be used for DIF after antigen retrieval. However, complement staining has not been satisfactory. We standardized DIF using proteinase-K for antigen retrieval in FFPE renal biopsies. A pilot study was conducted on known cases of membranous glomerulonephritis (MGN, membranoproliferative type-1 (MPGN-1, immunoglobulin A nephropathy (IgAN, and anti-glomerular basement disease (anti-GBM. Immunofluorescence panel included fluorescein isothiocyanate (FITC conjugated IgG, IgA, IgM, complements (C3 and C1q, light chains (kappa, lambda and fibrinogen antibodies. After standardization of the technique, 75 renal biopsies and 43 autopsies cases were stained. Out of 43 autopsy cases, immune-complex mediated glomerulonephritis (GN was confirmed in 18 cases (Lupus nephritis-11, IgAN-6, MGN-1, complement-mediated dense deposit disease (DDD-1 and monoclonal diseases in 4 cases (amyloidosis-3, cast nephropathy-1. Immune-mediated injury was excluded in 17 cases (focal segmental glomerulosclerosis -3, crescentic GN-6 [pauci-immune-3, anti-GBM-3], thrombotic microangiopathy-5, atherosclerosis-3. Renal biopsies (n-75 where inadequate or no frozen sample was available; this technique classified 52 mesangiocapillary pattern as MPGN type-1-46, DDD-2 and (C3GN-4. Others were diagnosed as IgAN-3, lupus nephritis-2, MGN-4, diffuse proliferative glomerulonephritis (DPGN-1, Non-IC crescentic GN-1, monoclonal diseases-3. In nine cases, DIF on FFPE tissue could not help in making diagnosis. Proteinase-K enzymatic digestion of FFPE renal biopsies can unmask complements (both C3 and C1q in immune-complexes mediated and complement-mediated diseases. This method showed good results on autopsy tissues archived for as long as 15 years.

Disease characterization of systemic lupus erythematosus (SLE) patients in Quebec.

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Ng, R; Bernatsky, S; Rahme, E

2017-08-01

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an array of organ manifestations that can appear during flares and disappear during remissions. The objectives of this study were: (i) to examine SLE manifestation groups longitudinally in an SLE cohort; and (ii) to assess the association between early antimalarial treatment and renal manifestations. Methods Seven SLE manifestation groups-cutaneous, hematologic, lung, musculoskeletal, neuropsychiatric, serositis, renal-were tracked using Kaplan-Meier survival curves in an incident SLE cohort from Quebec health administrative data ( n = 2010). A subgroup with provincial drug insurance coverage was followed over time to examine the association between early antimalarial treatment (within three months after SLE diagnosis) and renal manifestations using a Cox proportional hazards survival model. Results Cutaneous manifestations was the most common manifestation at SLE diagnosis (30.0%, 95% CI: 27.7-32.2%). About two-thirds (66.2%, 95% CI: 63.4-68.9%) of patients had evidence of at least one SLE manifestation at diagnosis, which increased to 87.2% (95% CI: 84.2-90.3%) by the end of follow-up. After adjusting for age, sex, early concomitant systemic steroid therapy, Charlson comorbidity index, primary care visits in the year prior and other SLE manifestations at baseline, no statistically significant association was established between antimalarial therapy and renal manifestations. Conclusion This study provides insight regarding organ manifestations within a population-based sample. Most patients identified with SLE had other diagnostic evidence that supports an underlying diagnosis of SLE. No protective effects for antimalarial agents against renal manifestations could be established in this population-based cohort.

Correlation between the trajectory of systolic blood pressure and new renal damage in a nonhypertensive population.

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Wang, Zhi-Jun; Jia, Dao; Tian, Jun; Liu, Jie; Li, Li-Jie; Huang, Yu-Ling; Cao, Xin-Ying; Ning, Chun-Hong; Zhao, Quan-Hui; Yu, Jun-Xing; Zhang, Rui-Ying; Zhang, Ya-Jing; Gao, Jing-Sheng; Wu, Shou-Ling

2017-10-01

This study aims to investigate the correlation between the trajectory of systolic blood pressure (SBP) and new renal damage in a nonhypertensive population. This prospective cohort study included a total of 14 382 nonhypertensive individuals, employees of Kailuan Group of Companies, who took part in five healthy examinations in 2006-2007, 2008-2009, 2010-2011, 2012-2013, and 2014-2015, and had complete data. These individuals were divided into four groups according to the different trajectories of SBP: low-low, low-stable, middle-high, and high-high groups. The correlation between the trajectory of SBP and new renal damage in a nonhypertensive population was analyzed using a multivariate Cox's proportional hazard regression model. (a) A total of 14 382 individuals had complete data and the average age of these individuals was 44.6±10.8 years. Among these, 10 888 (75.7%) individuals were men and 3494 (24.3%) individuals were women. (b) These individuals were divided into four groups according to different trajectories of blood pressure: low-low group, accounting for 13.15% (blood pressure was group, accounting for 53.91% (blood pressure was between 115 and 116 mmHg); middle-high group, accounting for 28.77% (blood pressure was between 125 and 131 mmHg); and high-high group, accounting for 4.6% (blood pressure was between 126 and 151 mmHg). (c) With the increase in the trajectory of SBP, the detection rate of renal damage increased gradually. From the low-low group to the high-high group, the detection rates of estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m were 2.3, 2.4, 3.6, and 4.3%, respectively; the positive rates of urinary protein were 1.7, 2.9, 3.8, and 5.5%, respectively; and the detection rates of eGFR less than 60 ml/min/1.73 m or positive urinary protein were 4, 5.2, 7.3, and 9.3%, respectively (Pgroup, the risk of eGFR less than 60 ml/min/1.73 m increased by nearly 1.5 times in the high-high group and in

[Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

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Kotyla, Przemysław; Kucharz, Eugeniusz J

2012-01-01

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

An unusual presentation of juvenile lupus nephritis

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Malleshwar Bottu

2016-01-01

Full Text Available The incidence of juvenile lupus varies widely ranging between 4 and 250 per 100,000 population. Most common organ involvement in juvenile lupus is kidney. Neurological, cutaneous and hematological involvements are also involved. Skeletal muscle involvement in the form of myositis is rare. Myositis as presenting manifestation in juvenile lupus is also unusual. Herein, we report one such case wherein myositis preceded the onset of lupus nephritis

X-ray phase-contrast tomography of renal ischemia-reperfusion damage.

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Astrid Velroyen

Full Text Available The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV. To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94. Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

Clinical profile of patients with biopsy proven lupus nephritis at a tertiary care hospital from Northern Pakistan, 1995 to 2012.

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Ali, Akhtar; Mehmood, Anjum; Ali, Muhammad Usman

2017-01-01

TTo highlight the clinical spectrum of biopsy-proven lupus nephritis by analysing any variations in its histological subtypes across gender, varying age groups, serum creatinine levels and anti-double stranded deoxyribonucleic acid levels. This retrospective, observational study was conducted at the Lady Reading Hospital in collaboration with the Fauji Foundation Hospital, Peshawar, Pakistan, and comprised patient records of biopsy-proven lupus nephritis from 1995 to 2012. The cases were analysed according to clinical presentations and histological pattern of systemic lupus erythematosus nephritis. EpiData 3.1 and SPSS 17 were used for data analyses. Of the 2,000 renal biopsies performed, lupus nephritis was found in 74(3.7%) cases. Of them, 63(85.1%) were females and 11(14.9%) males. The mean age of the cases was 23.88±9.73 years (range: 10-55 years). Class IV lupus nephritis was seen in 38(51.4%) patients, followed by Class II in 15(20.3%), Class III in 10(13.5%), Class V and VI in 4(5.4%) each and Class I in 3(4.1%). Out of the combined Class III and IV cases, 25(52.08%) had serum creatinine levels of >1.2 mg/dL, whereas positive anti-double stranded deoxyribonucleic acid titers up to 50 IU/L were seen in all of the 48(100%) such patients. Overall, microscopic haematuria was found in 52(70.3%) cases, followed by arthralgia in 40(54.1%). Moreover, 32(50.8%) females and 6(54.5%) males had Type IV nephritis. Class VI lupus nephritis, in particular, were significantly more prominent in 31-40 years of age group when compared to other histological subtypes and age groups (p=0.0096, odds ratio: 23.25, 95% confidence interval: 2.15-251.21). Female predominance was observed in all histological sub-types of lupus nephritis. Class IV lupus was the most common histological pattern. Microscopic haematuria was the most common clinical presentation.

Patients affected by a new variant of endemic pemphigus foliaceus have autoantibodies colocalizing with MYZAP, p0071, desmoplakins 1-2 and ARVCF, causing renal damage.

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Abreu-Velez, A M; Howard, M S; Yi, H; Florez-Vargas, A A

2018-05-16

We have previously reported that about 30% of patients affected by a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia (termed El Bagre-EPF or pemphigus Abreu-Manu) have systemic compromise. In the current study, we focused on studying autoreactivity to the kidney and its pathological correlations. To investigate patients with El Bagre-EPF for renal compromise. We performed a case-control study, enrolling 57 patients with El Bagre-EPF and 57 controls from the endemic area, matched by age, sex, race, work activity, demographics and comorbidities. We took skin and renal biopsies; performed direct and indirect immunofluorescence, immunohistochemistry (IHC), confocal microscopy, immunoblotting, direct and indirect immune electron microscopy; and tested kidney function in all living patients. We also used IHC to study seven kidney autopsy samples. Of the 57 patients, 19 had autoantibodies to kidney, with polyclonal reactivity (P EPF have polyclonal autoantibodies to kidney. The kidneys showed a mixed histological pattern resembling lupus nephritis, with a diffuse proliferative Class IV (G) global diffuse pattern in active lesions, and additional interposition of membranoproliferative glomerulonephritis. © 2018 British Association of Dermatologists.

Causes and predictors of mortality in hospitalized lupus patient in Sarawak General Hospital, Malaysia.

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Teh, C L; Ling, G R

2013-01-01

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.

[Jinshuibao capsule combined losartan potassium intervened early renal damage of hypertension patients of yin and yang deficiency: a clinical research].

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Zhang, Cheng-Qiu; Yin, Ji-Qing; Xin, Qing; Wang, Ya-Qin; Ge, Zhi-Ming

2013-06-01

To observe the effects of Jinshuibao Capsule (JC) combined losartan potassium on some indices of early renal damage of hypertension patients of yin and yang deficiency syndrome (YYDS), such as levels of serum cystatin C (Cys C), beta2-microglobulin (beta2-MG), hypersensitive C-reactive protein (hs-CRP), uric acid (UA), blood pressure, blood lipids, and fasting blood glucose (FBG), and to explore their protective effects on early renal damage of hypertension patients and on the metabolisms of blood lipids and blood glucose. Totally 106 hypertension patients of YYDS were randomly assigned to two groups, 53 patients in the control group (treated by losartan potassium) and 53 patients in the treatment group (treated by JC + losartan potassium). The treatment lasted for 16 weeks. The serum changes of UA, Cys C, beta2-MG, hs-CRP, blood lipids [including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C)], and FBG levels were measured to evaluate the renal protective effects and to assess their effect on the metabolisms of blood lipids and blood glucose. Compared with before treatment in the same group, the systolic blood pressure (SBP) decreased in the two groups after treatment, showing statistical difference (P 0.05). The diastolic blood pressure (DBP) was not obviously declined in the two groups after treatment, showing no statistical difference. Compared with before treatment in the same group, the LDL-C level decreased obviously after treatment in the control group. But there was no obvious change in FBG, TC, HDL-C, and TG in the control group, showing no statistical difference when compared with before treatment (P 0.05). Compared with before treatment in the same group, the levels of UA, Cys C, beta2-MG, and hs-CRP all decreased in the two groups, showing statistical difference (P < 0.05, P < 0.01). The SCr level decreased in the treatment group more obviously after treatment

Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations.

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Jeremiah, Nadia; Neven, Bénédicte; Gentili, Matteo; Callebaut, Isabelle; Maschalidi, Sophia; Stolzenberg, Marie-Claude; Goudin, Nicolas; Frémond, Marie-Louis; Nitschke, Patrick; Molina, Thierry J; Blanche, Stéphane; Picard, Capucine; Rice, Gillian I; Crow, Yanick J; Manel, Nicolas; Fischer, Alain; Bader-Meunier, Brigitte; Rieux-Laucat, Frédéric

2014-12-01

Innate immunity to viral infection involves induction of the type I IFN response; however, dysfunctional regulation of this pathway leads to inappropriate inflammation. Here, we evaluated a nonconsanguineous family of mixed European descent, with 4 members affected by systemic inflammatory and autoimmune conditions, including lupus, with variable clinical expression. We identified a germline dominant gain-of-function mutation in TMEM173, which encodes stimulator of type I IFN gene (STING), in the affected individuals. STING is a key signaling molecule in cytosolic DNA-sensing pathways, and STING activation normally requires dimerization, which is induced by 2'3' cyclic GMP-AMP (cGAMP) produced by the cGAMP synthase in response to cytosolic DNA. Structural modeling supported constitutive activation of the mutant STING protein based on stabilized dimerization. In agreement with the model predictions, we found that the STING mutant spontaneously localizes in the Golgi of patient fibroblasts and is constitutively active in the absence of exogenous 2'3'-cGAMP in vitro. Accordingly, we observed elevated serum IFN activity and a type I IFN signature in peripheral blood from affected family members. These findings highlight the key role of STING in activating both the innate and adaptive immune responses and implicate aberrant STING activation in features of human lupus.

Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk

DEFF Research Database (Denmark)

Hesselvig, J Halskou; Ahlehoff, O; Dreyer, L

2017-01-01

Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed...

Renal hemodynamics in uranyl acetate-induced acute renal failure of rabbits

International Nuclear Information System (INIS)

Sudo, M.; Honda, N.; Hishida, A.; Nagase, M.

1977-01-01

The role of renal hemodynamic alterations in the curtailment of renal function was studied in rabbits with uranyl acetate-induced acute renal failure. The day following the i.v. injection of uranyl acetate (2 mg/kg of body wt), renal blood flow (RBF) and clearance of creatinine (Ccr) decreased to approximately 60 and 20% of controls, respectively. Intracortical fractional flow distribution, estimated by radioactive microsphere method, did not change. The extraction ratio of para-aminohippurate (EPAH) decreased and the renal extraction of sodium (CNa/Ccr) increased, with minimal structural change in the kidney. Urine output increased two to three times that of the control. After three days oliguria appeared despite complete recovery of RBF. The zonal flow redistributed toward the deep cortex. CCr and EPAH reached their minimums, concomitantly with tubular necrosis and intratubular casts. After seven days animals could be divided into the oliguric and diuretic groups. CCr and EPAH were higher in the diuretic group, while there was no significant difference in RBF and the flow distribution between groups. Regeneration of damaged tubular cells was found in the diuretic group but not in the oliguric group. The findings suggest the minor roles of RBF and the intracortical flow distribution, and a fundamental role of back leakage of filtrate across damaged tubular epithelium in the maintenance of reduced CCR and urine output during the oliguric stage in rabbits with uranyl acetate-induced renal failure

Daño renal cortical en niños con primera infección del tracto urinario alto Cortical renal damage in children with a first infection of the high urinary tract

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Tulio Antonio Amaya Sorto

2012-03-01

.Introduction: between the 5 and the 22 % of children suffering acute pyelonephritis will develop a renal scar. Objective: to describe the clinical-epidemiological features of the cortical renal damage in children with a first infection of high urinary tract. Methods: a longitudinal, prospective and observational study was conducted on the cicatricial renal damage admitted in the Nephrology services of the "William Soler" University Children Hospital from January 1, 2008 to December 31, 2009. Fifty patients were diagnosed and 38 fulfilled the inclusion criteria to study. Patients had a mean age of 18 months and underwent renal ultrasound during the acute phase of disease and static renal scintigraphy between 6 and 12 months after the acute picture, to specify exactly the cortical renal injury. In cases of renal scar, lack or decrease of the radioactive drug capture (99mTc-DMSA authors carried out miction uretrocystography to specify exactly the presence of vesicoureteral reflux. Results: twenty six patients (73.7 % are females, 17 (44.7 % aged under 6 months, 17 (44.7 % have between 6 and 36 months and 4 (10.6 % > 3 years old. The urinary infection was atypical in 23 (60.5 % and as a isolated germ the Escherichia coli in 33 (86.8 %. Ultrasound of acute phase demonstrated a renal pelvis dilation in 3 (7.9 % and renal asymmetry in 1 (2.6 %. In 2 patients (5.2 % there was renal scar and in 11 (28.4 % an decreased function of the renal cortex. The miction uretrocystography demonstrated the presence of grade III vesicoureteral reflux in a girl, who also had a renal scar. There was not relation between the onset of symptoms, the onset of therapeutics and the cortical injury. Conclusions: the risk factors to develop a post-pyelonephritis renal scar were: female sex, be aged under 3 and grade III vesicoureteral reflux.

Overlap of Ankylosing Spondylitis and Systemic Lupus Erythematosus: A case report

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Mahmood Akbaryan

2016-04-01

Full Text Available Ankylosing spondylitis is a typical, very heritable incendiary joint inflammation, influencing principally the spine and pelvis. Inflammatory arthritis in ankylosing spondylitis causes pain and stiffness and progressively leads to new bone formation and ankylosis (fusion of affected joints. Systemic lupus erythematosus (SLE, lupus is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. There are few reports of coexistence of Ankylosing spondylitis and Systemic lupus erythematosus which firmly emphasis on an overlap phenomenon between these two disorders. A 30 year old woman was admitted to our hospital due to signs of butterfly-shaped rash on her cheeks, which became prominent after exposure to sunlight and severe inflammatory low-back pain. About ten year earlier, AS had been diagnosed and treatment started with non-steroidal anti-inflammatory drug (NSAID. To the best of our knowledge, the present case is one of 10 reported cases of coexistence of these two disorders in English literature. The coexistence of these two diseases with different genetic backgrounds and clinical symptoms may implicate the importance of shared environmental factors.

Clinical correlates and outcomes in a group of Puerto Ricans with systemic lupus erythematosus hospitalized due to severe infections

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Jordán-González, Patricia; Shum, Lee Ming; González-Sepúlveda, Lorena

2018-01-01

Objective: Infections are a major cause of morbidity and mortality in systemic lupus erythematosus. Clinical outcomes of systemic lupus erythematosus patients hospitalized due to infections vary among different ethnic populations. Thus, we determined the outcomes and associated factors in a group of Hispanics from Puerto Rico with systemic lupus erythematosus admitted due to severe infections. Methods: Records of systemic lupus erythematosus patients admitted to the Adult University Hospital, San Juan, Puerto Rico, from January 2006 to December 2014 were examined. Demographic parameters, lupus manifestations, comorbidities, pharmacologic treatments, inpatient complications, length of stay, readmissions, and mortality were determined. Patients with and without infections were compared using bivariate and multivariate analyses. Results: A total of 204 admissions corresponding to 129 systemic lupus erythematosus patients were studied. The mean (standard deviation) age was 34.7 (11.6) years; 90% were women. The main causes for admission were lupus flare (45.1%), infection (44.0%), and initial presentation of systemic lupus erythematosus (6.4%). The most common infections were complicated urinary tract infections (47.0%) and soft tissue infections (42.0%). In the multivariate analysis, patients admitted with infections were more likely to have diabetes mellitus (odds ratio: 4.20, 95% confidence interval: 1.23–14.41), exposure to aspirin prior to hospitalization (odds ratio: 4.04, 95% confidence interval: 1.03–15.80), and higher mortality (odds ratio: 6.00, 95% confidence interval: 1.01–35.68) than those without infection. Conclusion: In this population of systemic lupus erythematosus patients, 44% of hospitalizations were due to severe infections. Patients with infections were more likely to have diabetes mellitus and higher mortality. Preventive and control measures of infection could be crucial to improve survival in these patients.

The effect of a concomitant renal injury on the outcome of colonic trauma.

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Oosthuizen, G V; Weale, R; Kong, V Y; Bruce, J L; Urry, R J; Laing, G L; Clarke, D L

2017-12-06

The management of colon injuries has steadily evolved over the course of the last half century. So too has the management of renal trauma. It is not clear from the literature as to whether concomitant colon and renal injuries carry increased risk of morbidity and mortality, and whether this combination of injuries necessitates a specifically tailored management approach. A retrospective review was carried out for the period January 2012 to December 2016. All patients over the age of 18 years who were subjected to laparotomy for penetrating trauma (gunshot wounds or stab wounds) and who sustained an intra-operatively proven colonic injury were included in this study. Operative management and outcomes were investigated. A direct comparison was made between patients with a combined colonic and renal injury and those with only a colonic injury. Over the five-year period a total of 268 patients sustained a colonic injury. The 239 patients with a colonic injury (Group A) were compared to the 29 patients with a combined colonic and renal injury (Group B). Regarding the management of the colonic injuries, there were no differences in the rates of primary repair, anastomosis, exteriorization, or damage control surgery between groups A and B. As for the management of the renal injury, 14 were not explored at laparotomy; in 12 a nephrectomy was performed and in 3 the renal injury was repaired. The nephrectomy cohort were more likely to have undergone damage control surgery, to be admitted to ICU, to receive a colostomy, and had higher mortality. While there was no difference in the need for damage control surgery or mortality between groups, Group B had a significantly greater need for ICU admission. Morbidity was similar between the two groups - in particular, there was no difference in the rates of either gastro-intestinal complications or acute kidney injury between the two groups. In patients with combined colon and renal injuries, it seems reasonable to treat each organ

Nephroprotective Effect of Bauhinia tomentosa Linn against Cisplatin-Induced Renal Damage.

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Kannan, Narayanan; Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

2016-01-01

Cisplatin (CP) is an important chemotherapeutic drug used for the treatment of a wide variety of solid tumors. However, clinical use of CP has been limited due to its adverse effect of nephrotoxicity. In the present study, we evaluate the nephroprotective effect of Bauhinia tomentosa against CP-induced renal damage in rats. Administration of methonolic extract of B. tomentosa (250 mg/kg b.w.) results in a significant increase in antioxidant enzymes including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, treatment with B. tomentosa increased body weight and relative organ weight when compared with that of the CP-induced control group. Moreover, treatment with B. tomentosa extract significantly decreased lipid peroxidation(LPO), serum urea, and creatinine when compared with the CP-induced control group. Thus, the present study highlights the potential role of B. tomentosa and its use as a new protective strategy against CP-induced nephrotoxicity.

Dynamic renal scintigraphy at hydronephrosis

International Nuclear Information System (INIS)

Petrov, T.; Chukov, I.; Svrakova, E.

1998-01-01

The aim of the study was to estimate the clinical relevance and accuracy of dynamic renal scintigraphy (DRS) in case of obstructed kidneys as hydronephrosis is among the complications at different renal diseases, like nephrolithiasis and urolithiasis. Twenty-one patients mainly with unilateral hydronephrosis were studied. DRS with 99m Tc-MAG3 or 99m Tc-EC was done and quantitative parameters of the morphological and functional status of every kidney were assessed. At 24 % of the patients accumulation curves typical for obstructed by hydronephrosis kidneys were obtained. At 38 % the type of renograms of the affected kidneys was intermediate one, closer to that at the cases with nephrosclerosis, with lower uptake and severe parenchymal changes. The rest 38 % of the cases showed normal renograms or slightly delayed downslope. DRS is a very precise and sensitive method for evaluation of the degree of kidney damage in cases with hydronephrosis

DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury.

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Eun Lee, Jee; Kim, Jung Eun; Lee, Mi Hwa; Song, Hye Kyoung; Ghee, Jung Yeon; Kang, Young Sun; Min, Hye Sook; Kim, Hyun Wook; Cha, Jin Joo; Han, Jee Young; Han, Sang Youb; Cha, Dae Ryong

2016-05-01

Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury.

ESRD from lupus nephritis in the United States, 1995-2010.

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Sexton, Donal J; Reule, Scott; Solid, Craig; Chen, Shu-Cheng; Collins, Allan J; Foley, Robert N

2015-02-06

While ESRD from lupus nephritis (ESLN) increased in the United States after the mid-1990s and racial disparities were apparent, current trends are unknown. Retrospective US Renal Data System data (n=1,557,117) were used to calculate standardized incidence ratios (standardized to 1995-1996) and outcomes of ESLN (n=16,649). For events occurring after initiation of RRT, follow-up ended on June 30, 2011. Overall ESLN rates (95% confidence intervals [95% CIs]) in 1995-1996 were 3.1 (2.9 to 3.2) cases per million per year. Rates were higher for subgroups characterized by African-American race (11.1 [95% CI, 10.3 to 11.9]); other race (4.9 [95% CI, 4.0 to 5.8]); female sex (4.9 [95% CI, 4.6 to 5.2]); and ages 20-29 years (4.9 [95% CI, 4.4 to 5.4]), 30-44 years (4.6 [95% CI, 4.2 to 5.0]), and 45-64 years (4.0 [95% CI, 3.7 to 4.4]). Standardized incidence ratios for the overall population in subsequent biennia were 1.19 (1.14 to 1.24) in 1997-1998, 1.17 (1.12 to 1.22) in 1999-2000, 1.17 (1.12 to 1.22) in 2001-2002, 1.21 (1.16 to 1.26) in 2003-2004, 1.18 (1.13 to 1.23) in 2005-2006, 1.16 (1.11 to 1.21) in 2007-2008, and 1.05 (1.01 to 1.09) in 2009-2010, respectively. During a median (interquartile range) follow-up of 4.4 (6.3) years, 42.6% of patients with ESLN died, 45.3% were listed for renal transplant, and 28.7% underwent transplantation. Patients with ESLN were more likely than matched controls to be listed for and to undergo transplantation, and mortality rates were similar. Among patients with ESLN, African Americans were less likely to undergo transplantation (adjusted hazard ratio, 0.54 [0.51 to 0.58]) and more likely to die prematurely (adjusted hazard ratio, 1.23 [1.17 to 1.30]). While ESLN appears to have stopped increasing in the last decade, racial disparities in outcomes persist. Copyright © 2015 by the American Society of Nephrology.

Circulating surfactant protein D is decreased in systemic lupus erythematosus

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Hoegh, Silje Vermedal; Voss, Anne; Sorensen, Grith Lykke

2009-01-01

Objective. Deficiencies of innate immune molecules like mannan binding lectin (MBL) have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Surfactant protein D (SP-D) and MBL belong to the same family of innate immune molecules - the collectins, which share important...

A Study on Clinical and Pathologic Features in Lupus Nephritis with Mainly IgA Deposits and a Literature Review

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Liu Hongyan

2013-01-01

Full Text Available Objective. To study the clinical and pathologic features of systemic lupus erythematosus (SLE that has atypical lupus nephritis (LN with mainly IgA deposits. Methods. We searched the SLE patients who had nephritis with mainly IgA deposits in our hospital and selected the information including clinical manifestations, laboratory tests, treatments, and prognosis. Results. From January 2009 to June 2012, 5 patients were definitely diagnosed as SLE according to both 1982 and 2009 ACR classification criteria. But renal biopsy showed that all cases had mainly IgA deposits and were free of IgG, C1q, and fibrinogen-related antigen deposits under immunofluorescent microscopy, which did not match with typical LN. There were 2 males and 3 females, aging from 31 to 64 years and with an average of years. The 5 cases had multiple-system involvements, mainly the renal system. Compared to primary IgAN, the atypical LN showed some differences: older than primary IgAN, more women than men, no previous infection history, lower incidence of serum IgA elevation, and ACL positive rate as high as 100%. Conclusion. Nephritis with mainly IgAN deposits, as an atypical LN, may be a special subtype of SLE.

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

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Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

2016-08-01

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Analysis on the change of T lymphocyte subsets and NK cells in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Yao Yanhua; Chen Zhiwei; Deng Yingsu; Gu Guohao; Gao Chun; Yu Yunxia

2006-01-01

Objective: To investigate the relationship between the peripheral blood lymphocyte subsets, disease activity and renal impairment in patients with systemic lupus erythematosus (SLE). Methods: T lymphocyte subsets and NK cells from the peripheral blood of 78 patients who suffered SLE were measured, and then the relationship between disease activity, renal symptoms and the states of cellular immunology were analysed. Results: CD 8 + and CD 3 + cells were significantly decreased in the peripheral blood from those patients with active stage of SLE compared to remission phase, while the CD 4 + cells and CD 4 + /CD 8 + ratio did not. And NK cells, but not CD 3 + , CD 8 + cells or CD 4 + /CD 8 + and CD 8 + cells may correlate the the disease activity of SLE patients, but CD 4 + and ratio CD 4 + CD 8 + can not reflect disease activity. While the reduction of NK cells may have relationship with renal suffering. (authors)

Relative Contributions of B Cells and Dendritic Cells from Lupus-Prone Mice to CD4+ T Cell Polarization.

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Choi, Seung-Chul; Xu, Zhiwei; Li, Wei; Yang, Hong; Roopenian, Derry C; Morse, Herbert C; Morel, Laurence

2018-05-01

Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4 + T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts. This expansion was dependent on CD86 and IL-6 expression and mapped to the Sle1 lupus-susceptibility locus. In vivo, TC B cells promoted greater differentiation of CD4 + T cells into Th1 and follicular helper T cells than did B6 B cells, but they limited the expansion of Foxp3 regulatory CD4 + T cells to a greater extent than did B6 B cells. Finally, when normal B6 CD4 + T cells were introduced into Rag1 -/- mice, TC myeloid/stromal cells caused their heightened activation, decreased Foxp3 regulatory CD4 + T cell differentiation, and increased renal infiltration of Th1 and Th17 cells in comparison with B6 myeloid/stromal cells. The results show that B cells from lupus mice amplify inflammatory CD4 + T cells in a nonredundant manner with myeloid/stromal cells. Copyright © 2018 by The American Association of Immunologists, Inc.

Low capacity of erythrocytes to bind with immune complexes via C3b receptor in patients with systemic lupus erythematosus: correlation with pathological proteinuria

International Nuclear Information System (INIS)

Nojima, Y.; Terai, C.; Minota, S.; Takano, K.; Miyakawa, Y.; Takaku, F.

1985-01-01

Erythrocytes from 51 patients with systemic lupus erythematosus and 75 controls were tested for the capacity to bind aggregated human gamma-globulin labeled with radioiodine in the presence of complement. Both in patients and controls, a trimodal distribution of binding capacity was observed. Low (less than 9% of the added radioactivity), intermediate (9-17%), and high binding (more than 17%) were observed in 13, 58, and 29% in controls and in 49, 43 and 8% in lupus patients. The low binding capacity of erythrocytes persisted even after patients entered remission following steroid therapy. A genetic control of binding capacity was supported by familial surveys. Prevalence of pathological proteinuria was significantly higher in patients with low binding capacity than those with intermediate or high binding capacity (16/25 vs 7/26, P less than 0.01). These results indicate that an impaired physiological disposal of immune complexes via the erythrocyte C3b receptor in lupus patients may contribute to the development of renal involvement

Estrogen in cardiovascular disease during systemic lupus erythematosus.

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Gilbert, Emily L; Ryan, Michael J

2014-12-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against cardiovascular risk factors in

Estrogen in Cardiovascular Disease during Systemic Lupus Erythematosus

Science.gov (United States)

Gilbert, Emily L.; Ryan, Michael J.

2015-01-01

Purpose Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a major cardiovascular disease risk factor, and its prevalence is markedly increased in women with SLE. Estrogen has traditionally been implicated in SLE disease progression because of the prevalence of the disease in women; however, its role in cardiovascular risk factors such as hypertension is unclear. The objective of this review is to discuss evidence for the role of estrogen in both human and murine SLE with emphasis on the effect of estrogen on cardiovascular risk factors, including hypertension. Methods PubMed was used to search for articles with terms related to estradiol and SLE. The references of retrieved publications were also reviewed. Findings The potential permissive role of estrogen in SLE development is supported by studies from experimental animal models of lupus in which early removal of estrogen or its effects leads to attenuation of SLE disease parameters, including autoantibody production and renal injury. However, data about the role of estrogens in human SLE are much less clear, with most studies not reaching firm conclusions about positive or negative outcomes after hormonal manipulations involving estrogen during SLE (ie, oral contraceptives, hormone therapy). Significant gaps in knowledge remain about the effect of estrogen on cardiovascular risk factors during SLE. Studies in women with SLE were not designed to determine the effect of estrogen or hormone therapy on blood pressure even though hypertension is highly prevalent, and risk of premature ovarian failure could necessitate use of hormone therapy in women with SLE. Recent evidence from an experimental animal model of lupus found that estrogen may protect against

THE CAROLINA LUPUS STUDY (CLU)

Science.gov (United States)

Carolina Lupus (CLU) Study, an epidemiologic study of risk factors for systemic lupus erythematosus (SLE). SLE is a severe, chronic, systemic autoimmune disease that disproportionately affects women and African-Americans. The CLU Study focuses on measures of endogenous hormone ex...

A rare case of unilateral discoid lupus erythematosus mimicking lupus vulgaris.

Science.gov (United States)

Verma, Parul; Pathania, Sucheta; Kubba, Asha

2017-11-08

Discoidlupus erythematosus (DLE) is a chronic type of cutaneous lupus erythematosus which can present in various morphologies, and the diagnosis can be rather confounding. Prompt evaluation and treatment is necessary to prevent disfigurement and systemic involvement associated with DLE. The following case presented a diagnostic dilemma as the lesion mimicked lupus vulgaris. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Diagnosis of renal disease in rabbits.

Science.gov (United States)

Harcourt-Brown, Frances Margaret

2013-01-01

There are differences in renal anatomy and physiology between rabbits and other domestic species. Neurogenic renal ischemia occurs readily. Reversible prerenal azotemia may be seen in conjunction with gut stasis. Potentially fatal acute renal failure may be due to structural kidney damage or post-renal disease. Chronic renal failure is often associated with encephalitozoonosis. Affected rabbits cannot vomit and often eat well. Weight loss, lethargy, and cachexia are common clinical signs. Polydypsia/polyuria may be present. Derangements in calcium and phosphorus metabolism are features of renal disease. Radiography is always indicated. Urolithiasis, osteosclerosis, aortic and renal calcification are easily seen on radiographs. Copyright © 2013 Elsevier Inc. All rights reserved.

Glomerular Filtration Rate Estimation in Renal and Non-Renal Solid Organ Transplantation

DEFF Research Database (Denmark)

Hornum, Mads; Feldt-Rasmussen, Bo

2017-01-01

Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like hyperten......Following transplantation (TX) of both renal and non-renal organs, a large proportion of patients have renal dysfunction. There are multiple causes for this. Chronic nephrotoxicity and high doses of calcineurin inhibitors are important factors. Preoperative and perioperative factors like...... hypertension, hypotension, drugs and infections may play a causative role as well. Organ-specific causes include hepatorenal syndrome, cirrhosis, low cardiac function, low respiratory function and diabetes developed both before and after TX. It is important to be able to perform precise and valid measurements...... rate methods for use in renal and non-renal TX....

Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

DEFF Research Database (Denmark)

Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

2017-01-01

to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect......Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads...... in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...

Pro: Cyclophosphamide in lupus nephritis

NARCIS (Netherlands)

Kallenberg, Cees G. M.

Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up

The renal transcriptome in experimental hypertension

NARCIS (Netherlands)

Wesseling, S.

2007-01-01

The renal transcriptome in experimental hypertension The kidneys importantly determine blood pressure. Kidney dysfunction can result in hypertension, which in turn leads to renal damage. In primary hypertension the cause is unknown. The condition is polygenic, however, which genetic defects cause

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

Science.gov (United States)

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes : A 12-week, randomized, double-blind, placebo-controlled trial

NARCIS (Netherlands)

Tonneijck, Lennart; Smits, Mark M.; Muskiet, Marcel H A; Hoekstra, Trynke; Kramer, Mark H H; Danser, A. H Jan; Ter Wee, Piet M.; Diamant, Michaela; Joles, Jaap A.; Van Raalte, Daniël H.

2016-01-01

OBJECTIVE To investigate effects of dipeptidyl peptidase-4 inhibitor (DPP-4I) sitagliptin or glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide treatment on renal hemodynamics, tubular functions, and markers of renal damage in overweight patients with type 2 diabetes without chronic kidney

Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

Science.gov (United States)

Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

2003-12-01

The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

Health-related quality of life in patients with systemic lupus erythematosus: development and validation of a lupus specific symptom checklist

NARCIS (Netherlands)

Grootscholten, C.; Ligtenberg, G.; Derksen, R. H. W. M.; Schreurs, K. M. G.; de Glas-Vos, J. W.; Hagen, E. C.; van den Wall Bake, A. W. L.; Huizinga, T. W. J.; van den Hoogen, F. H. J.; Bijl, M.; van Houwelingen, J. C.; Snoek, F. J.; Berden, J. H. M.

2003-01-01

Reliable and sensitive measures are needed to evaluate the quality of life (QoL) in patients with systemic lupus erythematosus (SLE). No lupus specific questionnaires are available. This study describes the development and validation of a disease-specific questionnaire for lupus patients, which

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

Science.gov (United States)

Azizoddin, D R; Weinberg, S; Gandhi, N; Arora, S; Block, J A; Sequeira, W; Jolly, M

2018-04-01

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

The cellular basis of renal injury by radiation

International Nuclear Information System (INIS)

Williams, M.V.

1986-01-01

This review with substantial bibliography summarises renal assay techniques available and discusses the histological and functional studies leading to differing opinions between the belief that vascular injury provides a general explanation of the late effects of radiotherapy and the opposing view that parenchymal cell damage is more important. It is proposed that the link between glomerular and tubular function obscures the primary site of injury and that radiation injury will result in a reduction of functioning nephron mass by primary damage to the tubules or glomeruli. Compensatory renal vasodilation would close a positive feedback loop. Radiation could also cause direct vascular injury; decreased renal perfusion and hypertension would result. Again sensitisation to hypertensive vascular damage would close a feedback loop. (UK)

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus

DEFF Research Database (Denmark)

Petri, Michelle; Orbai, Ana-Maria; Alarcón, Graciela S

2012-01-01

The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new...

Renal denervation by intravascular ultrasound: Preliminary in vivo study

Science.gov (United States)

Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

2012-10-01

Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

Renal Vein Reconstruction for Harvesting Injury in Kidney Transplantation

Directory of Open Access Journals (Sweden)

Birkan Bozkurt

2014-03-01

Full Text Available Kidney transplantation is the best treatment choice in the end-stage renal disease. In the renal transplantation, renal vein damage or shortness which occurs during cadaveric or living donor nephrectomy causes technical difficulties for surgeons. The lack of the donors already especially cadaveric, the acquirement of the graft, gets very much importance. In this report, it is aimed to share the clinical experiment by which it seen, how anastomosis can become appropriate by using the renal vein which is damaged in the way that anastomosis cannot be done anyway by using cadaveric vena cava graft. The renal vein brought to length for anostomosis which is repaired by using cadaveric vena cava graft, is anastomosed successfully by becoming an end-to-side of the external iliac vein of the recipient. Vascular anastomoses are applied easily in technique. The time of the warm ischemia was under 2 hours and the kidney was functional in the post-operative period. Renal vein trombosis was not observed. The renal vein damage occured during cadaveric or living donor nephrectomy, can be repaired by some methods. In the kidneys in which vein requirement is done, the success rates are rather high although acute tubular necrosis and delayed function can be seen more.

Ecthyma gangrenosum like lesions in disseminated mycobacterial tuberculosis infection in a renal transplant recipient

Directory of Open Access Journals (Sweden)

Navjyot Kaur

2017-01-01

Full Text Available Ecthyma gangrenosum (EG is a relatively rare skin manifestation that is most commonly described in Pseudomonas aeruginosa bacteremia. It is more frequently seen in immunocompromised individuals. We report a case of 60-year-old renal transplant recipient on triple immunosuppressants and diabetes mellitus type 2 on insulin therapy who developed EG-like lesions due to disseminated mycobacterial tuberculosis (MTB infection. To the best of our knowledge, this is the first case report of EG-like lesions associated with disseminated kochs.

Altered expression of signalling lymphocyte activation molecule receptors in T-cells from lupus nephritis patients-a potential biomarker of disease activity.

Science.gov (United States)

Stratigou, Victoria; Doyle, Anne F; Carlucci, Francesco; Stephens, Lauren; Foschi, Valentina; Castelli, Marco; McKenna, Nicola; Cook, H Terence; Lightstone, Liz; Cairns, Thomas D; Pickering, Matthew C; Botto, Marina

2017-07-01

The aim was to investigate whether the signalling lymphocyte activation molecule (SLAM) signalling pathways contribute to LN and whether SLAM receptors could be valuable biomarkers of disease activity. Peripheral blood mononuclear cells from 30National Research Ethics Service SLE patients with biopsy-proven LN were analysed by flow cytometry. Clinical measures of disease activity were assessed. The expression of the SLAM family receptors on T-cell subpopulations [CD4, CD8 and double negative (DN) T cells] was measured and compared between lupus patients with active renal disease and those in remission. The frequency of CD8 T cells expressing SLAMF3, SLAMF5 and SLAMF7 was significantly lower in LN patients who were in remission. In contrast, these subsets were similar in patients with active renal disease and in healthy individuals. Patients with active nephritis had an increased percentage of circulating monocytes, consistent with a potential role played by these cells in glomerular inflammation. Changes in the frequency of DN T cells positive for SLAMF2, SLAMF4 and SLAMF7 were observed in lupus patients irrespective of the disease activity. We detected alterations in the cellular expression of the SLAM family receptors, but these changes were less obvious and did not reveal any specific pattern. The percentage of DN T cells expressing SLAMF6 could predict the clinical response to B-cell depletion in patients with LN. Our study demonstrates altered expression of the SLAM family receptors in SLE T lymphocytes. This is consistent with the importance of the SLAM-associated pathways in lupus pathogenesis. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Single side damage simulations and detection in beam-like structures

International Nuclear Information System (INIS)

Zhou, Yun-Lai; Perera, R; Wahab, M Abdel; Maia, N; Sampaio, R; Figueiredo, E

2015-01-01

Beam-like structures are the most common components in real engineering, while single side damage is often encountered. In this study, a numerical analysis of single side damage in a free-free beam is analysed with three different finite element models; namely solid, shell and beam models for demonstrating their performance in simulating real structures. Similar to experiment, damage is introduced into one side of the beam, and natural frequencies are extracted from the simulations and compared with experimental and analytical results. Mode shapes are also analysed with modal assurance criterion. The results from simulations reveal a good performance of the three models in extracting natural frequencies, and solid model performs better than shell while shell model performs better than beam model under intact state. For damaged states, the natural frequencies captured from solid model show more sensitivity to damage severity than shell model and shell model performs similar to the beam model in distinguishing damage. The main contribution of this paper is to perform a comparison between three finite element models and experimental data as well as analytical solutions. The finite element results show a relatively well performance. (paper)

Renal anomalies associated with imperforate anus : case reports

International Nuclear Information System (INIS)

Nahar, Nurun; Nisa, Lutfun; Alam, F.; Karim, M.A.

2002-01-01

Four cases of renal anomaly associated with anorectal malformation are illustrated here. The findings highlight the importance of early diagnosis of renal disorders in the pediatric with congenital anomalies in order to prevent irreversible damage to the kidneys. The high sensitivity of radionuclide diagnostic imaging methods in the early diagnosis of renal disorders and evaluation of renal function in children is emphasized.(author)

Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case-control study.

Science.gov (United States)

Viazzi, Francesca; Ramesh, Ganesan; Jayakumar, Calpurnia; Leoncini, Giovanna; Garneri, Debora; Pontremoli, Roberto

2015-06-01

Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated. To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case-control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR). USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002). USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD.

Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era.

Science.gov (United States)

Del Sordo, Rachele; Brugnano, Rachele; Covarelli, Carla; Fiorucci, Gioia; Falzetti, Franca; Barbatelli, Giorgio; Nunzi, Emidio; Sidoni, Angelo

2017-01-01

Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure. Glomerulopathy associated with PMF is rarely described, ranging from 1 month to 18 years from diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in PMF-related glomerulopathy, associated with EMH, without renal failure, in a patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite treatment, the patient died 7 months after renal biopsy. Nephrologists still know very little about this topic and there is no homogeneous data about incidence, pathogenesis, and optimal treatment of this poor prognostic PMF-associated nephrotic syndrome. We focus on data in the literature in the hope of stimulating hematologists, nephrologists, pathologists to future studies about the natural history of renal involvement, useful for optimal management of this rare pathology.

The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

Science.gov (United States)

Al Sawah, S; Daly, R P; Foster, S A; Naegeli, A N; Benjamin, K; Doll, H; Bond, G; Moshkovich, O; Alarcón, G S

2017-01-01

Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus. © The Author(s) 2016.

Pulmonary arterial hypertension as a manifestation of lupus erythematosus

Energy Technology Data Exchange (ETDEWEB)

Stark, P; Sargent, E N; Boylen, T; Jaramillo, D

1987-08-01

We present five patients with systemic lupus erythematosus (SLE) who developed pulmonary arterial hypertension and cor pulmonale in the course of their disease. The clinical features, as well as, the radiological manifestations of this rare manifestation of SLE are discussed. A vasculitic process is the most likely cause of this complication. Therapy is ineffective and the prognosis is poor.

Aggressive periodontitis in a patient with chronic cutaneous lupus erythematosus: a case report.

Science.gov (United States)

Tietmann, Christina; Bissada, Nabil F

2006-05-01

Lupus erythematosus is considered to be a high risk factor for periodontitis. As an autoimmune disease of unknown origin, cutaneous lupus erythematosus (CLE) is subdivided into 3 categories: chronic (CCLE), subacute (SCLE), and acute (ACLE). While the ACLE has a high prevalence of conjunctive periodontal lesions, aggressive periodontitis in patients with CCLE has been rarely reported. This article describes the case of a patient diagnosed with aggressive periodontitis. Three months after the diagnosis of periodontitis, the patient experienced advancing hair loss (alopecia), pale fingers and toes, as well as edema in the legs and around the eyes. Skin biopsy showed follicular hyperkeratosis with perivascular mononuclear cell infiltrate. Colliquation of the basal cells, thickening of the basal lamina, and vacuolar degeneration of basal keratinocytes were also found. A lupus band test was positive, and diagnosis of CCLE was established. Three months following the treatment of lupus with antimalarial agents, the periodontal condition became stable with no further exacerbation or progression of the existing periodontitis. An 11-month postsurgical follow-up revealed stable periodontal and general medical conditions. A patient's medical history should be re-evaluated in the event of recurrence of periodontal lesions refractory to periodontal treatment. The control of systemic conditions like lupus erythematosus is essential for a good prognosis in the treatment of periodontitis as well as for the general health of the patient.

Neuropsychiatric Systemic Lupus Erythematosus

Science.gov (United States)

Popescu, Alexandra; Kao, Amy H

2011-01-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus. PMID:22379459

Renal involvement in dogs with babesiosis

Directory of Open Access Journals (Sweden)

R.G. Lobetti

2001-07-01

Full Text Available Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium, fractional clearance of sodium (FcNa and potassium (FcK, urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n =10 and 3 groups of babesiosis cases were studied: mild uncomplicated (n =10, severe uncomplicated (n = 11, and complicated (n = 9. All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serumelectrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant

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